Compounds exhibiting thrombopoietin receptor agonism

ABSTRACT

A compound represented by the general formula (I): 
     
       
         
         
             
             
         
       
     
     wherein R 1  is a hydrogen atom, a halogen atom, or the like; R 2 , R 3 , and R 4  are each independently a hydrogen atom, a halogen atom, C1-C15 alkyl optionally substituted with one or more C1-C12 alkyloxy or the like, or the like; R 5  is a hydrogen atom or the like; R 6  and R 7  are a hydrogen atom or the like; R 8  is C1-C3 alkyl or the like; R 9  is a hydrogen atom or the like), a prodrug, a pharmaceutically acceptable salt, or solvate thereof.

TECHNICAL FIELD

The present invention relates to compounds exhibiting thrombopoietinreceptor agonism.

BACKGROUND ART

Thrombopoietin, polypeptide cytokine composed of 332 amino acids,activates the production of platelets by stimulating the differentiationand proliferation of megakaryocytes through the receptor and is expectedas a medicine for hemopathy accompanied with the unusual number ofplatelets, for example, thrombocytopenia and the like. DNA sequencesencoding the thrombopoietin receptor have been described inNon-Patent 1. Low molecular peptides having an affinity for thethrombopoietin receptor is also known in Patent 1 and Patent 2, butthese peptide derivatives are not generally practical for oraladministration.

As a low molecule compound having an affinity to the thrombopoietinreceptor, 1,4-benzodiazepine derivatives are described in Patent 3 andPatent 4, 1-azonaphthalene derivatives are described in Patent 5,N-(4-phenyl-1,3-thiazol-2-yl)carboxamide derivatives are described inPatent 6, Patent 7, Patent 8, Patent 9, and Patent 10.

Patent 1: JP98/72492

Patent 2: WO96/40750

Patent 3: JP99/1477

Patent 4: JP99/152276

Patent 5: WO00/35446

Patent 6: WO01/07423

Patent 7: WO01/53267

Patent 8: WO02/059099

Patent 9: WO02/059100

Patent 10: JP981287634

Non-Patent 1: Proc. Natl. Acad. Sci., 89, 5640-5644 (1992)

DISCLOSURE OF INVENTION

The object of the present invention is to prepare pharmaceuticalcompositions exhibiting thrombopoietin receptor agonism and provideorally administrable platelet production modifiers.

In the above situation, the inventors of the present invention havefound that the following compounds exhibit strong thrombopoietinreceptor agonism.

The present invention relates to:

1) A compound represented by the general formula (I):

wherein R¹ is a hydrogen atom, a halogen atom, C1-C6 alkyl, or C1-C12alkyloxy;

R², R³, and R⁴ are each independently a hydrogen atom, a halogen atom,C1-C15 alkyl optionally substituted with one or two substituent(s)selected from substituent group A, C2-C15 alkenyl optionally substitutedwith one or two substituent(s) selected from substituent group A, C2-C15alkynyl optionally substituted with one or two substituent(s) selectedfrom substituent group A, C3-C8 cycloalkyl, C1-C15 alkyloxy optionallysubstituted with one or two substituent(s) selected from substituentgroup A, or phenyl optionally substituted with one or two substituent(s)selected from substituent group A;

R⁵ is a hydrogen atom, a halogen atom, C1-C3 alkyl, C1-C3 alkyloxy, ormorpholono;

R⁶ is a hydrogen atom, a halogen atom, or C1-C3 alkyl;

R⁷ is a halogen atom or C1-C3 alkyl;

R⁸ is a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy;

configuration of double bond substituted with R⁸ is E configuration or Zconfiguration;

R⁹ is a hydrogen atom or C1-C6 alkyl; or

R¹ and R⁵ are taken together with the adjacent carbon atoms may form a 5to 8 membered ring which may contain a heteroatom(s) and/or anunsaturated bond(s), wherein the ring may be substituted with one or twoC1-C8 alkyl;

provided that when R² and R³ are a chlorine atom, R⁶ is not a hydrogenatom;

substituent group A consists of a halogen atom, C3-C8 cycloalkyl, C3-C8cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C12alkyloxy, C2-C12 alkenyloxy, C2-C12 alkynyloxy, C3-C8 cycloalkyl-C1-C8alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy,di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy;

a pharmaceutically acceptable salt, or solvate thereof,2) A compound of 1), wherein both of R⁶ and R⁷ are a fluorine atom or achlorine atom, a pharmaceutically acceptable salt, or solvate thereof,3) A compound of 1) or 2), wherein R⁸ is a hydrogen atom or C1-C3alkyloxy, a pharmaceutically acceptable salt, or solvate thereof,4) A compound of any one of 1) to 3), wherein R⁸ is methyl or methyloxy,a pharmaceutically acceptable salt, or solvate thereof,5) A compound of any one of 1) to 4), wherein R² is C1-C15 alkyloptionally substituted with one or two substituent(s) selected fromsubstituent group A, C2-C15 alkynyl optionally substituted with one ortwo substituent(s) selected from substituent group A, or C1-C15 alkyloxyoptionally substituted with one or two substituent(s) selected fromsubstituent group A, a pharmaceutically acceptable salt, or solvatethereof,6) A compound of any one of 1) to 4), wherein R² is C1-C12 alkyloptionally substituted with one or two C1-C8 alkyloxy, and both of R³and R⁴ are a hydrogen atom, a pharmaceutically acceptable salt, orsolvate thereof,7) A compound represented by the general formula (II):

wherein R^(A) is a hydrogen atom, C1-C12 alkyloxy, C1-C8 alkyloxy-C1-C8alkyloxy or (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy;R^(B) is C1-C14 alkyl optionally substituted with one or twosubstituent(s) selected from substituent group B, C2-C14 alkynyloptionally substituted with one or two substituent(s) selected fromsubstituent group B, C3-C8 cycloalkyl, C1-C14 alkyloxy optionallysubstituted with one or two substituent(s) selected from substituentgroup B, phenyl, or naphthyl;

R^(C) is a hydrogen atom, a halogen atom, C1-C6 alkyl, or C1-C12alkyloxy;

R^(D) is a hydrogen atom, a halogen atom, C1-C3 alkyl, C1-C3 alkyloxy,or morpholino;

R⁶ and R⁷ are each independently a halogen atom or C1-C3 alkyl;

R⁸ is a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy;

configuration of double bond substituted with R⁸ is E configuration or Zconfiguration;

substituent group B consists of a halogen atom, C3-C8 cycloalkyl, C3-C8cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy,di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; apharmaceutically acceptable salt, or solvate thereof,

8) A compound of 7), wherein both of R⁶ and R⁷ are a fluorine atom or achlorine atom, a pharmaceutically acceptable salt, or solvate thereof,9) A compound of 7) or 8), wherein R⁸ is methyl or methyloxy, apharmaceutically acceptable salt, or solvate thereof,10) A compound of any one of 7) to 9), wherein R^(C) is a fluorine atomor C1-C3 alkyloxy, a pharmaceutically acceptable salt, or solvatethereof,11) A compound of any one of 7) to 10), wherein R^(A) is C1-C8 alkyloxy;R^(B) is C1-C11 alkyl optionally substituted with one or twosubstituent(s) selected from substituent group B; C2-C11 alkynyloptionally substituted with one or two substituent(s) selected fromsubstituent group B, a pharmaceutically acceptable salt, or solvatethereof,12) A compound of 7), wherein R^(C) is a fluorine atom or C1-C3alkyloxy, R^(D) is a hydrogen atom or C1-C3 alkyloxy, both of R⁶ and R⁷are a fluorine atom or a chlorine atom, R⁸ is methyl or methyloxy, R^(A)is C1-C3 alkyloxy, R^(B) is C8-C12 alkyl optionally substituted with oneor two substituent(s) selected from substituent group B, apharmaceutically acceptable salt, or solvate thereof,13) A compound represented by the general formula (III):

wherein R^(E) is C1-C15 alkyl optionally substituted with one or twosubstituent(s) selected from substituent group C, C2-C15 alkynyloptionally substituted with one or two substituent(s) selected fromsubstituent group C, or C1-C15 alkyloxy optionally substituted with oneor two substituent(s) selected from substituent group C;

Z is straight-chain C1-C4 alkylene optionally substituted with C1-C8alkyl, which may contain an optionally substituted a heteroatom(s) orstraight-chain C2-C4 alkenylene optionally substituted with C1-C8 alkyl,which may contain an optionally substituted heteroatom(s);

R⁶ and R⁷ are each independently a halogen atom or C1-C3 alkyl;

R⁸ is a halogen atom, CJ-C3 alkyl, or CJ-C3 alkyloxy;

configuration of double bond substituted with R⁸ is E configuration or Zconfiguration;

substituent group C consists of a halogen atom, C3-C8 cycloalkyl, C3-C8cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy,di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy;

a pharmaceutically acceptable salt, or solvate thereof,14) A compound of 13), wherein both of R⁶ and R⁷ are a fluorine atom ora chlorine atom, a pharmaceutically acceptable salt, or solvate thereof,15) A compound of 13) or 14), wherein R⁸ is methyl or methyloxy, apharmaceutically acceptable salt, or solvate thereof,16) A compound of any one of 13) to 15), wherein Z is C1-C4 alkylene,—O—(C1-C3 alkylene)-, or —(C1-C3 alkylene)-O—, a pharmaceuticallyacceptable salt, or solvate thereof,17) A compound of any one of 13) to 16), wherein R^(E) is C1-G1 alkyloptionally substituted with one or two substituent(s) selected fromsubstituent group C, C2-C10 alkynyl optionally substituted with one ortwo substituent(s) selected from substituent group C, or C1-C10 alkyloxyoptionally substituted with one or two substituent(s) selected fromsubstituent group C, a pharmaceutically acceptable salt, or solvatethereof,18) A compound of 13), wherein both of R⁶ and R⁷ are a fluorine atom ora chlorine atom, R⁸ is methyl or methyloxy, R^(E) is C1-C8 alkyloptionally substituted with one or two C1-C6 alkyloxy, Z is C1-C2alkylene, a pharmaceutically acceptable salt, or solvate thereof, 19) Acompound represented by the general formula (II-A):

wherein R^(C) is a hydrogen atom, a halogen atom, C1-C6 alkyl, or C1-C12alkyloxy;

R^(D) is a hydrogen atom, a halogen atom, C1-C3 alkyl, C1-C3 alkyloxy,or morpholino;

RF is C1-C14 alkyl optionally substituted with one or two substituent(s)selected from substituent group D, C2-C14 alkenyl optionally substitutedwith one or two substituent(s) selected from substituent group D, C2-C14alkynyl optionally substituted with one or two substituent(s) selectedfrom substituent group D, C1-C14 alkyloxy optionally substituted withone or two substituent(s) selected from substituent group C, C3-C8cycloalkyl, or phenyl optionally substituted with one or twosubstituent(s) selected from substituent group D;

R⁶ and R⁷ are each independently a halogen atom or C1-C3 alkyl;

R⁸ is a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy;

substituent group D consists of a halogen atom, C3-C8 cycloalkyl, C3-C8cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy,di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; apharmaceutically acceptable salt, or solvate thereof,

20) A compound of 19), wherein both of R⁶ and R⁷ are a fluorine atom ora chlorine atom, a pharmaceutically acceptable salt, or solvate thereof,21) A compound of claim 19), wherein R⁸ is methyl or methyloxy, apharmaceutically acceptable salt, or solvate thereof,22) A compound of 19), wherein R^(C) is a fluorine atom or C1-C3alkyloxy, a pharmaceutically acceptable salt, or solvate thereof,23) A compound of any one of 19) to 22), wherein R^(E) is C1-C14 alkyloptionally substituted with one or two substituent(s) selected fromsubstituent group D, C2-C14 alkynyl optionally substituted with one ortwo substituent(s) selected from substituent group D, or C1-C14 alkyloxyoptionally substituted with one or two substituent(s) selected fromsubstituent group D, a pharmaceutically acceptable salt, or solvatethereof,24) A pharmaceutical composition containing a compound as an activeingredient, a pharmaceutically acceptable salt, or solvate thereof ofany one of 1) to 23),25) A pharmaceutical composition containing a compound as an activeingredient, a pharmaceutically acceptable salt, or solvate thereof ofany one of 1) to 23), which is exhibiting thrombopoietin receptoragonism,26) A platelet production modifier which contains a compound as anactive ingredient, a pharmaceutically acceptable salt, or solvatethereof of any one of 1) to 23),27) Use of a compound, a pharmaceutically acceptable salt, or solvatethereof of any one of 1) to 23) for preparation of a pharmaceuticalcomposition for modifying a platelet production,28) A method for modifying a platelet production of a mammal, includinga human, which comprises administration to said mammal of a compound, apharmaceutically acceptable salt, or solvate thereof of any one of 1) to23) in a pharmaceutically effective amount.

In the present specification, the term “halogen atom” means fluorineatom (fluoro), chlorine atom (chloro), bromine atom (bromo), and iodineatom (iodo).

In the present specification, nitrogen atom, oxygen atom, sulfur atom,and the like are exemplified as “heteroatom”.

In the present specification, the term “alkyl” employed alone or incombination with other term includes a straight- or branched chain alkylhaving contains forward-mentioned number of carbon. Methyl, ethyl,n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl,isopentyl, neo-pentyl, n-hexyl, isohexyl, n-heptyl, n-octyl, n-nonyl,n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl,and the like are exemplified as “alkyl”.

In the present specification, the term “alkenyl” employed alone or incombination with other term includes a straight- or branched chainalkenyl having forward-mentioned number of carbon. Ethenyl,2-propen-1-yl, 3-butene-1-yl, 14-pentadecen-1-yl, and like like areexemplified as “alkenyl”.

In the present specification, the term “alkynyl” employed alone or incombination with other term includes a straight- or branched chainalkynyl having forward-mentioned number of carbon. Ethynyl,1-propyn-1-yl, 1-butyn-1-yl, 1-pentyn-1-yl, 1-hexyn-1-yl, 1-heptyn-1-yl,1-decyn-1-yl, 1-pentadecyn-1-yl, and the like are exemplified as“alkynyl”.

In the present specification, the term “cycloalkyl” employed alone or incombination with other term includes a mono-carbocyclic group havingforward-mentioned number of carbon. Cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like areexemplified as “cycloalkyl”.

In the present specification, the term “cycloalkenyl” employed alone orin combination with other term includes a mono-carbocyclic group havingforward-mentioned number of carbon and one or more double bond(s).Cyclopropenyl, 1-cyclobuten-1-yl, 1-cyclopenten-1-yl, 1-cyclohexen-1-yl,1-cyclohepten-1-yl, 1-cycloocten-1-yl, and the like are exemplified as“cycloalkenyl”.

In the present specification, the term “naphthyl” means 1-naphthyl or2-naphthyl.

In the present specification, the term “pyridyl” means 2-pyridyl,3-pyridyl or 4-pyridyl.

In the present specification, the term “oxolanyl” means 2-oxolanyl or3-oxolanyl.

In the present specification, the term “alkyloxy” employed alone or incombination with other term includes alkyloxy having forward-mentionednumber of carbon. Methyloxy, ethyloxy, n-propyloxy, isopropyloxy,n-butyloxy, isobutyloxy, sec-butyloxy, tert-butyloxy, n-pentyloxy,isopentyloxy, neo-pentyloxy, n-hexyloxy, isohexyloxy, n-heptyloxy,n-octyloxy, n-nonyloxy, n-decyloxy, n-undecyloxy, n-dodecyloxy,n-pentadecyloxy, and the like are exemplified as “alkyloxy”.

In the present specification, the term “haloalkyloxy” employed alone orin combination with other term includes the above-mentioned “alkyloxy”substituted with one or more halogen atom(s). Chloromethyloxy,difluoromethyloxy, 2,2,2-trifluoroethyloxy, 3-chloropropyloxy,4-fluorobutyloxy, and the like are exemplified as “haloalkyloxy”.

In the present specification, the term “alkenyloxy” employed alone or incombination with other term includes the above-mentioned “alkenyl”substituted with one or more hydroxy. 2-Propenyloxy, 3-butenyloxy,4-octenyloxy, and the like are exemplified as “alkenyloxy”.

In the present specification, the term “alkynyloxy” employed alone or incombination with other term includes the above-mentioned “alkynyl”substituted with one or more hydroxy. 2-Propynnyloxy, 3-butynyloxy,4-octynyloxy, and the like are exemplified as “alkynyloxy”.

In the present specification, cylopropylmethyloxy, 2-cylopropylethyloxy,2-cylobutylethyloxy, 3-cylopentylpropyloxy, cylohexylmethyloxy,4-cylohexylbutyloxy, 8-cylooctyloctyloxy, and the like are exemplifiedas “C3-C8 cycloalkyl-C1-C8 alkyloxy”.

In the present specification, phenylmethyloxy, 2-phenylethyloxy,3-phenylpropyloxy, 4-phenylbutyloxy, 8-phenyloctyloxy, and the like areexemplified as “phenyl-C1-C8 alkyloxy”.

In the present specification, 1-naphthylmethyloxy, 2-naphthylmethyloxy,2-(1-naphthyl)ethyloxy, 3-(2-naphthyl)propyloxy, 4-(1-naphthyl)butyloxy,8-(2-naphthyl)octyloxy, and the like are exemplified as “naphthyl-C1-C8alkyloxy”.

In the present specification, 2-methyloxyethyloxy, 2-ethyloxyethyloxy,3-methyloxypropyloxy, 4-ethyloxybutyloxy, and the like are exemplifiedas “C1-C4 alkyloxy-C2-C4 alkyloxy”.

In the present specification, methyloxymethyloxy, 2-methyloxyethyloxy,2-ethyloxyethyloxy, 3-methyloxypropyloxy, 4-ethyloxybutyloxy,6-butyloxyhexyloxy, 8-octyloxyoctyloxy, and the like are exemplified as“C1-C8 alkyloxy-C1-C8 alkyloxy”.

In the present specification, 2-(methyloxymethyloxy)ethyloxy,2-(2-ethyloxyethyloxy)ethyloxy, 3-(2-methyloxyethyloxy)propyloxy,4-(2-ethyloxyethyloxy)butyloxy, and the like are exemplified as “(C1-C4alkyloxy-C2-C4 alkyloxy)C2-C4 alkyloxy”.

In the present specification, 2-(2-methyloxyethyloxy)ethyloxy,2-(2-ethyloxyethyloxy)ethyloxy, 3-(2-methyloxyethyloxy)propyloxy,4-(2-ethyloxyethyloxy)butyloxy, 8-(2-butyloxyethyloxy)octyloxy, and thelike are exemplified as “(C1-C8alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy”.

In the present specification, 1,3-di(methyloxy)-2-propyloxy,1,3-di(ethyloxy)-2-propyloxy, 1-ethyloxy-3-methyloxy-2-propyloxy, andthe like are exemplified as “di(C1-C8alkyloxy)C1-C8 alkyloxy”.

In the present specification, “oxolanyl-C1-C8 alkyloxy” means theabove-mentioned “C1-C8 alkyloxy” substituted with oxolanyl. Examples ofoxolanyl-C1-C8 alkyloxy includes 2-oxolanyletyloxy, 3-oxolanylpropyloxy,4-oxolanylbutyloxy, 8-oxolanyloctyloxy, and the like.

In the present specification, the term “cycloalkyloxy” employed alone orin combination with other term includes an oxygen atom substituted witha mono-carbocyclic group having forward-mentioned number of carbon.Cycloalkyloxy include cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,cyclohexyloxy, cyclooctynyloxy, and the like are exemplified as“cycloalkyloxy”.

In the present specification, the term “alkylthio” employed alone or incombination with other term includes a straight- or branched chainalkylthio having forward-mentioned number of carbon. Alkylthio includemethylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio,isobutylthio, sec-butylthio, tert-butylthio, n-pentylthio,isopentylthio, neo-pentylthio, n-hexyllhio, isohexylthio, n-heptylthio,n-octylthio, and the like are exemplified as “alkylthio”.

In the present specification, 2-methylthioethyloxy, 2-ethylthioethyloxy,3-methylthiopropyloxy, 4-ethylthiobutyloxy, 8-butylthiooctyloxy, and thelike are exemplified as “C1-C8 alkylthio-C1-C8 alkyloxy”.

In the present specification, the term “C1-C2 alkylene” means methyleneand ethylene.

In the present specification, the term “straight-chain C1-C4 alkylene”means straight-chain alkylene having one to four carbon atom(s).Methylene, ethylene, trimethylene, and tetramethylene are exemplified as“straight-chain C1-C4 alkylene”.

In the present specification, the term “C1-C3 alkylene” meansstraight-chain alkylene having one to three carbon atom(s). Methylene,ethylene, and trimethylene are exemplified as “C1-C3 alkylene”.

In the present specification, the term “straight-chain C1-C4 alkyleneoptionally substituted with C1-C8 alkyl, which may contain optionallysubstituted a heteroatom(s)” means straight-chain alkylene having one tofour carbon atom(s) which may contain optionally substituted one tothree heteroatom(s) optionally substituted with C1-C8 alkyl and thealkylene may be optionally substituted with C1-C8 alkyl. Examples are—CH₂—, —CH₂CH₂—, —CH(n-C4H₉)CH₂—, —CH(n-C6H₁₃)CH₂—, —CH(n-C₇H₁₅)CH₂—,—CH₂CH₂CH₂—, —CH₂CH₂CH₂CH₂—, —CH₂O—, —OCH₂—, —SCH₂—, —OCH₂O—,—OCH₂CH₂O—, —CH₂CH₂OCH₂CH₂—, and the like.

In the present specification, the term straight-chain C2-C4 alkenyleneoptionally substituted with C1-C8 alkyl, which may contain optionallysubstituted a heteroatom(s)” means straight-chain alkenylene having twoto four carbon atom(s) which may contain optionally substituted one tothree heteroatom(s) optionally substituted with C1-C8 alkyl and thealkenylene may be optionally substituted with C1-C8 alkyl. Examples are—CH═CH—, —O—CH═CH—, —S—CH═CH—, —O—CH═CH—O—, and the like.

In the present specification, C1-C8 alkyl is exemplified as “optionallysubstituted heteroatom”

In the present specification, cyclopentadiene, benzene, cyclohexadiene,cycloheptadiene, furan, thiophen, pyran, and the like are exemplified as“5 to 8 membered ring taken together with the adjacent carbon atomswhich may contain a heteroatom(s) and/or an unsaturated bond(s)”.

In the present specification, the term “amino optionally substitutedwith C1-C8 alkyl” means non-substituted amino and amino substituted withone or two C1-C8 alkyl. Examples are amino, monomethylamino,dimethylamino, ethylamino, diethylamino, and the like.

Preferable are a fluorine atom and a chlorine atom as “halogen atom” forR¹, R², R³, R⁴, R⁵, R^(C), and R^(D). Especially, a fluorine atom ispreferable.

Preferable are a fluorine atom and a chlorine atom as “halogen atom” forR⁶, R⁷, and R⁸.

Preferable are C1-C4 alkyl as “C1-C6 alkyl” for R¹, R⁹, and R^(C).Especially, methyl or ethyl is preferable.

Preferable is methyl as “C1-C3 alkyl” for R⁵, R⁶, R⁷, R⁸, and R^(D).

Preferable are C1-C8 alkyloxy as “C1-C12 alkyloxy” for R^(I) and R^(C).Especially, methyloxy or ethyloxy is preferable.

Preferable is methyloxy as “C1-C3 alkyloxy” for R⁵, R⁸, and R^(D).

Preferable is C1-C12 alkyl as “C1-C15 alkyl” of “C1-C15 alkyl optionallysubstituted with substituent(s) selected from substituent group A” forR², R³, and R⁴. Preferable are C5-C6 cycloalkyl, C1-C8 alkyloxy, C1-C4alkyloxy-C2-C4alkyloxy, (C1-C4 alkyloxy-C2-C4alkyloxy)C2-C4 alkyloxy, ormethylthio as “substituent(s) selected from substituent group A”.Preferable is one or two as “number(s) of substituent(s)”.

Preferable is a 5 to 6 membered ring which may contain a heteroatom(s)and/or an unsaturated bond(s) as “R¹ and R⁵ taken together with theadjacent carbon atoms may form a 5 to 8 membered ring which may containa heteroatom(s) and/or an unsaturated bond(s)”. Preferable are an oxygenatom, a sulfur atom, or a nitrogen atom as heteroatom. Preferable is oneas a number of heteroatom. Preferable is a double bond as an unsaturatedbond. Preferable is one as a number of double bond.

Preferable is C1-C8 alkyloxy as “C1-C12 alkyloxy” for R^(A).

Preferable is C1-C4 alkyloxy-C2-C4 alkyloxy as “C1-C8alkyloxy-C1-C8alkyloxy” for R^(A).

Preferable is (C1-C4 alkyloxy-C2-C4 alkyloxy)C2-C4 alkyloxy as “(C1-C8alkyloxy-C1-C8alkyloxy)C1-C8 alkyloxy” for R^(A).

Preferable is C1-C12 alkyl as “C1-C14 alkyl” of “straight- or branchedchain C1-C14 alkyl optionally substituted with substituent(s) selectedfrom substituent group B” for R^(B). Preferable are C5-C6 cycloalkyl,C1-C8 alkyloxy, C1-C4 alkyloxy-C2-C4alkyloxy, (C1-C4alkyloxy-C2-C4alkyloxy)C2-C4 alkyloxy, or methylthio as “substituent(s)selected from substituent group B”. Preferable is one as “number ofsubstituent(s)”.

Preferable is C1-C10 alkyl as “C1-C15 alkyl” of “straight- or branchedchain C1-C15 alkyl optionally substituted with substituent(s) selectedfrom substituent group C” for R^(E). Especially, C1-C8 alkyl ispreferable. Preferable are C5-C6 cycloalkyl, C1-C8 alkyloxy, C1-C4alkyloxy-C2-C4alkyloxy, (C1-C4 alkyloxy-C2-C4alkyloxy)C2-C4 alkyloxy, ormethylthio as “substituent(s) selected from substituent group C”.Especially, C1-C6 alkyloxy is preferable. Preferable is one or two as“number of substituent(s)”.

Preferable are C1-C4 alkylene, —O—(C1-C3 alkylene), (C1-C3 alkylene)-O—as “straight-chain C1-C4 alkylene optionally substituted with C1-C8alkyl, which may contain optionally substituted heteroatom” for Z.Especially, C1-C2 alkylene or —

OCH₂O-is preferable.

Substituents groups (Ia) to (Io) are shown as preferable substituent(s)groups for R¹ to R⁹ of the compound represented by general formula (I)

For R¹, (Ia) a hydrogen atom, a halogen atom, or C1-C6 alkyloxy, (Ib)halogen atom or C1-C6 alkyloxy.

For R², (Ic) C1-C15 alkyl substituted with one or same or different twosubstituent(s) selected from substituent group consists of (C5-C6cycloalkyl, C1-C8 alkyloxy, C1-C4 alkyloxy-C2-C4 alkyloxy, (C1-C4alkyloxy-C2-C4 alkyloxy)C2-C4 alkyloxy, and methylthio), C2-C15 alkynylsubstituted with one or same or different two substituent(s) selectedfrom substituent group consists of (C5-C6 cycloalkyl, C1-C8 alkyloxy,C1-C4 alkyloxy-C2-C4 alkyloxy, (C1-C4: alkyloxy-C2-C4 alkyloxy)C2-C4alkyloxy, and methylthio) or C1-C15 alkyloxy substituted with one orsame or different two substituent(s) selected from substituent groupconsists of (C5-C6 cycloalkyl, C1-C8 alkyloxy, C1-C4 alkyloxy-C2-C4alkyloxy, (C1-C4 alkyloxy-C2-C4 alkyloxy)C2-C4 alkyloxy, andmethylthio), (Id) C1-C15 alkyl substituted with one substituent selectedfrom substituent group consists of (C1-C8 alkyloxy and C1-C4alkyloxy-C2-C4 alkyloxy), C2-C15 alkynyl substituted with onesubstituent selected from substituent group consists of (C1-C8 alkyloxyand C1-C4 alkyloxy-C2-C4 alkyloxy), or C1-C15 alkyloxy substituted withone substituent selected from substituent group consists of (C1-C8alkyloxy and C1-C4 alkyloxy-C2-C4 alkyloxy), (Ie) C1-C15 alkylsubstituted with one C1-C8 alkyloxy, C2-C15 alkynyl substituted with oneC1-C8 alkyloxy, or C1-C15 alkyloxy substituted with one C1-C8 alkyloxy.

For R³, R⁴, and R⁵, (If) each independently a hydrogen atom or C1-C3alkyloxy.

For R¹ and R⁷, (Ig) each independently a halogen atom.

For R⁸, (Ih) a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy, (Ii) C1-C3alkyl or C1-C3 alkyloxy, (Ij) C1-C3 alkyl.

For R⁹, (Ik) a hydrogen atom.

Or, R¹ and R⁵ may form a (II) 5 to 6 membered ring taken together withthe adjacent carbon atoms which may contain an oxygen atom, (Im) 6membered carbocylic ring taken together with the adjacent carbon atoms,(In) 6 membered ring taken together with the adjacent carbon atoms whichcontains one oxygen atom.

Examples of preferable group of the compound represented by generalformula (I) contains [R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, R⁹]=[Ia, Ic, If,If, Ig, Ig, Ih, Ik], [Ia, Ic, If, If, If, Ig, Ig, Ii, Ik], [Ia, Ic, If,If, If, Ig, Ig, Ij, Ik], [Ia, Id, If, If, If, Ig, Ig, Ih, Ik], [Ia, Id,If, If, If, Ig, Ig, Ii, Ik], [Ia, Id, If, If, If, Ig, Ig, Ij, Ik], [Ia,Ie, If, If, If, Ig, Ig, Ih, Ik], [Ia, Ie, If, If, If, Ig, Ig, Ii, Ik],[Ia, Ie, If, If, If, Ig, Ig, Ij, Ik], [Ib, Ic, If, If, If, Ig, Ig, Ih,Ik], [Ib, Ic, If, If, If, Ig, Ig, Ii, Ik], [Ib, Ic, If, If, If, Ig, Ig,Ij, Ik], [Ib, Id, If, If, If, Ig, Ig, Ih, Ik], [Ib, Id, If, If, If, Ig,Ig, Ii, Ik], [Ib, Id, If, If, If, Ig, Ig, Ij, Ik], [Ib, Ie, If, If, If,Ig, Ig, Ih, Ik], [Ib, Ie, If, If, If, Ig, Ig, Ii, Ik], [Ib, Ie, If, If,If, Ig, Ig, Ij, Ik], or [R¹-R⁵, R², R³, R⁴, R⁶, R⁷, R⁸, R⁹]=[Il, Ic, If,If, Ig, Ig, Ih, Ik], [Il, Ic, If, If, Ig, Ig, Ii, Ik], [In, Ic, If, If,Ig, Ig, Ij, Ik], [Il, Id, If, If, Ig, Ig, Ih, Ik], [Il, Id, If, If, Ig,Ig, Ii, Ik], [Il, Id, If, If, Ig, Ig, Ij, Ik], [Il, Ie, If, If, Ig, Ig,Ih, Ik], [Il, Ie, If, If, Ig, Ig, Ii, Ik], [Il, Ie, If, If, Ig, Ig, Ij,Ik], [Im, Ic, If, If, Ig, Ig, Ih, Ik], [Im, Ic, If, If, Ig, Ig, Ii, Ik],[Im, Ic, If, Ig, Ig, Ij, Ik], [Im, Id, If, If, Ig, Ig, Ih, Ik], [Im, Id,If, If, Ig, Ig, Ii, Ik], [Im, Id, If, If, Ig, Ig, Ij, Ik], [Im, Ie, If,If, Ig, Ig, Ih, Ik], [Im, Ie, If, If, Ig, Ig, Ii, Ik], [Im, Ie, If, If,Ig, Ig, Ij, Ik], [In, Ic, If, If, Ig, Ig, Ih, Ik], [In, Ic, If, If, Ig,Ig, Ii, Ik], [In, Ic, If, If, Ig, Ig, Ij, Ik], [In, Id, If, If, Ig, Ig,Ih, Ik], [In, Id, If, If, Ig, Ig, Ii, Ik], [In, Id, If, If, Ig, Ig, Ij,Ik], [In, Ie, If, If, Ig, Ig, Ih, Ik], [In, Ie, If, If, Ig, Ig, Ii, Ik],[In, Ie, If, If, Ig, Ig, Ij, Ik].

Substituents groups (IIa) to (IIn) are shown as preferablesubstituent(s) groups for R⁶ to R⁸ and R^(A) to R^(D) of the compoundrepresented by general formula (II)

For R⁶ and R⁷, (IIa) each independently a halogen atom.

For R⁸, (IIb) a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy, (IIc)C1-C3 alkyl or C1-C3 alkyloxy, (IId) C1-C3 alkyl.

For R^(A), (IIe) a hydrogen atom, C1-C8 alkyloxy, or C1-C4alkyloxy-C2-C4 alkyloxy, (IIf) C1-C8 alkyloxy, (IIg) C1-C4alkyloxy-C2-C4 alkyloxy.

For R^(B), (IIh) C1-C14 alkyl substituted with one substituent selectedfrom substituent group consists of (a hydrogen atom, C1-C8 alkyloxy, andC1-C4 alkyloxy-C2-C4 alkyloxy), C2-C14 alkynyl substituted with onesubstituent selected from substituent group consists of (a hydrogenatom, C1-C8 alkyloxy, and C1-C4 alkyloxy-C2-C4 alkyloxy), or C1-C14alkyloxy substituted with one substituent selected from substituentgroup consists of (a hydrogen atom, C1-C8 alkyloxy, and C1-C4alkyloxy-C2-C4 alkyloxy), (IIi) C1-C14 alkyl, (IIj) C1-C14 alkylsubstituted with one C1-C8 alkyloxy, C2-C14 alkynyl substituted with oneC1-C8 alkyloxy, or C1-C14 alkyloxy substituted with one C1-C8 alkyloxy,(IIk) C1-C14 alkyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy,C2-C14 alkynyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy, orC1-C14 alkyloxy substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy.

For R^(C), (III) a hydrogen atom, a halogen atom, or C1-C6 alkyloxy,(IIm) halogen atom or C1-C6 alkyloxy.

For R^(D), (IIn) a hydrogen atom or C1-C3 alkyloxy.

Examples of preferable group of the compound represented by generalformula (II) contains [R⁶, R⁷, R⁸, R^(A), R^(B), R^(C), R^(D)]=[IIa,IIa, IIb, IIe, IIh, IIl, IIn], [IIa, IIa, IIb, IIe, IIh, IIm, IIn],[IIa, IIa, IIb, IIe, IIi, IIk, IIn], [IIa, IIa, IIb, IIe, IIi, IIm,IIn], [IIa, IIa, IIb, IIe, IIj, IIl, IIn], [IIa, IIa, IIb, IIe, IIj,IIm, IIn], [IIa, IIa, IIb, IIe, IIk, IIl, IIn], [IIa, IIa, IIb, IIe,IIk, IIm, IIn], [IIa, IIa, IIb, IIf, IIh, IIl, IIn], [IIa, IIa, IIb,IIf, IIh, IIm, IIn], [IIa, IIa, IIb, IIf, IIi, IIl, IIn], [IIa, IIa,IIb, IIf, IIi, IIm, IIn], [IIa, IIa, IIb, IIf, IIj, IIl, IIn], [IIa,IIa, IIb, IIf, IIj, IIm, IIn], [IIa, IIa, IIb, IIf, IIk, IIl, IIn],[IIa, IIa, IIb, IIf, IIk, IIm, IIn], [IIa, IIa, IIb, IIg, IIh, IIl,IIn], [IIa, IIa, IIb, IIg, IIh, IIm, IIn], [IIa, IIa, IIb, IIg, IIi,IIl, IIn], [IIa, IIa, IIb, IIg, IIi, IIm, IIn], [IIa, IIa, IIb, IIg,IIj, IIl, IIn], [IIa, IIa, IIb, IIg, IIj, IIm, IIn], [IIa, IIa, IIb,IIg, IIk, IIl, IIn], [IIa, IIa, IIb, IIg, IIk, IIm, IIn], [IIa, IIa,IIc, IIe, IIh, IIl, IIn], [IIa, IIa, IIc, IIe, IIh, IIm, IIn], [IIa,IIa, IIc, IIe, IIi, IIl, IIn], [IIa, IIa, IIc, IIe, IIi, IIm, IIn],[IIa, IIa, IIc, IIe, IIj, IIl, IIn], [IIa, IIa, IIc, IIe, IIj, IIm,IIn], [IIa, IIa, IIc, IIe, IIk, IIl, IIn], [IIa, IIa, IIc, IIe, IIk,IIm, IIn], [IIa, IIa, IIc, IIf, IIh, IIl, IIn], [IIa, IIa, IIc, IIf,IIh, IIm, IIn], [IIa, IIa, IIc, IIf, IIi, IIl, IIn], [IIa, IIa, IIe,IIf, IIi, IIm, IIn], [IIa, IIa, IIc, IIf, IIi, IIl, IIn], [IIa, IIa,IIc, IIf, IIj, IIm, IIn], [IIa, IIa, IIc, IIf, IIk, IIl, IIn], [IIa,IIa, IIe, IIf, IIk, IIm, IIn], [IIa, IIa, IIc, IIg, IIb, IIl, IIn],[IIa, IIa, IIc, IIg, IIh, IIm, IIn], [IIa, IIa, IIc, IIg, IIi, IIl,IIn], [IIa, IIa, IIc, IIg, IIi, IIm, IIn], [IIa, IIa, IIe, IIg, IIl,IIl, IIn], [IIa, IIa, IIc, IIg, IIj, IIm, IIn], [IIa, IIa, IIc, IIg,IIk, IIl, IIn], [IIa, IIa, IIc, IIg, IIk, IIm, IIn], [IIa, IIa, IId,IIe, IIh, IIl, IIn], [IIa, IIa, IId, IIe, IIh, IIm, IIn], [IIa, IIa,IId, IIe, IIi, IIl, IIn], [IIa, IIa, IId, IIe, IIi, IIm, IIn], [IIa,IIa, IId, IIe, IIj, IIl, IIn], [IIa, IIa, IId, IIe, IIj, IIm, IIn],[IIa, IIa, IId, IIe, IIk, IIl, IIn], [IIa, IIa, IId, IIe, IIk, IIm,IIn], [IIa, IIa, IId, IIf, IIh, IIn], [IIa, IIa, IId, IIf, IIh, IIm,IIn], [IIa, IIa, IId, IIf, IIi, IIl, IIn], [IIa, IIa, IId, IIf, IIi,IIm, IIn], [IIa, IIa, IId, IIf, IIj, IIl, IIn], [IIa, IIa, IId, IIf,IIj, IIm, IIn], [IIa, IIa, IId, IIf, IIk, IIl, IIn], [IIa, IIa, IId,IIf, IIk, IIm, IIn], [IIa, IIa, IId, IIg, IIh, IIl, IIn], [IIa, IIa,IId, IIg, IIh, IIm, IIn], [IIa, IIa, IId, IIg, IIl, IIn], [IIa, IIa,IId, IIg, IIi, IIm, IIn], [IIa, IIa, IId, IIg, IIj, IIl, IIn], [IIa,IIa, IId, IIg, IIj, IIm, IIn], [IIa, IIa, IId, IIg, IIk, IIl, IIn],[IIa, IIa, IId, IIg, IIk, IIn].

Substituents groups (IIIa) to (IIIn) are shown as preferablesubstituent(s) groups for R⁶ to R⁸, R^(E), and Z of the compoundrepresented by general formula (III)

For R⁶ and R⁷, (IIIa) each independently a halogen atom.

For R⁸, (IIIb) a halogen atom, CJ-C3 alkyl, or C1-C3 alkyloxy, (IIIc)C1-C3 alkyl or C1-C3 alkyloxy, (IId) C1-C3 alkyl.

For R^(E), (IIIe) C1-C15 alkyl substituted with one substituent selectedfrom substituent group consists of (C1-C8 alkyloxy and C1-C4alkyloxy-C2-C4 alkyloxy), C2-C15 alkynyl substituted with onesubstituent selected from substituent group consists of (C1-C8 alkyloxyand C1-C4 alkyloxy-C2-C4 alkyloxy), or C1-C15 alkyloxy substituted withone substituent selected from substituent group consists of (C1-C8alkyloxy and C1-C4 alkyloxy-C2-C4 alkyloxy), (IIIf) C1-C15 alkylsubstituted with one C1-C8 alkyloxy, C2-C15 alkynyl substituted with oneC1-C8 alkyloxy, or C1-C15 alkyloxy substituted with one C1-C8 alkyloxy,(IIIg) C1-C15 alkyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy,C2-C15 alkynyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy, orC1-C15 alkyloxy substituted with one CT-C4 alkyloxy-C2-C4 alkyloxy.

For Z, (IIIh) ethylene or oxymethylene, (IIIi) ethylene.

Examples of preferable group of the compound represented by generalformula (III) contains [R⁶, R⁷, R⁸, R^(E), Z]=[IIIa, IIIa, IIIb, IIIe,IIIh], [IIIa, IIIa, IIIb, IIIe, IIIi], [IIIa, IIIa, IIIb, IIIf, IIIh],[IIIa, IIIa, IIIb, IIIf, IIIi], [IIIa, IIIa, IIIb, IIIg, IIIh], [IIIa,IIIa, IIIb, IIIg, IIIi], [IIIa, IIIa, IIIc, IIIe, IIIh], [IIIa, IIIa,IIIc, IIIe, IIIi], [IIIa, IIIa, IIIc, IIIf, IIIh], [IIIa, IIIa, IIIc,IIIf, IIIi], [IIIa, IIIa, IIIc, IIIg, IIIh], [IIIa, IIIa, IIIc, IIIg,IIIi], [IIIa, IIIa, IIId, IIIe, IIIh], [IIIa, IIIa, IIId, IIIe, IIIi],[IIIa, IIIa, IIId, IIIf, IIIh], [IIIa, IIIa, IIId, IIIf, IIIi], [IIIa,IIIa, IIId, IIIg, IIIh], [IIIa, IIIa, IIId, IIIg, IIIi].

Substituents groups (II-Aa) to (II-Al) are shown as preferablesubstituent(s) groups for R⁶ to R⁸, R^(C), R^(D), and RF of the compoundrepresented by general formula (II-A)

For R⁶ and R⁷, (II-Aa) each independently a halogen atom.

For R⁸, (II-Ab) a halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy, (III-Ac)C1-C3 alkyl or C1-C3 alkyloxy, (II-Ad) C1-C3 alkyl.

For R^(C), (II-Ae) a halogen atom or C1-C6 alkyloxy, (III-Af) halogenatom, (II-Ag) C1-C6 alkyloxy.

For R^(D), (1-Ah) a hydrogen atom or C1-C3 alkyloxy, (II-Ai) a hydrogenatom.

For R^(F), (II-Aj) C1-C14 alkyl substituted with one substituentselected from substituent group consists of (C1-C8 alkyloxy and C1-C4alkyloxy-C2-C4 alkyloxy), C2-C14 alkynyl substituted with onesubstituent selected from substituent group consists of (C1-C8 alkyloxyand C1-C4 alkyloxy-C2-C4 alkyloxy), or C1-C14 alkyloxy substituted withone substituent selected from substituent group consists of (C1-C8alkyloxy and C1-C4 alkyloxy-C2-C4 alkyloxy), (II-Ak) C1-C14 alkylsubstituted with one C1-C8 alkyloxy, C2-C14 alkynyl substituted with oneC1-C8 alkyloxy, or C1-C14 alkyloxy substituted with one C1-C8 alkyloxy,(II-Al) C1-C14 alkyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy,C2-C14 alkynyl substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy, orC1-C14 alkyloxy substituted with one C1-C4 alkyloxy-C2-C4 alkyloxy.

Examples of preferable group of the compound represented by generalformula (II-A) contains [R⁶, R⁷, R⁸, R^(C), R^(D), R^(F)]=[II-Aa, II-Aa,II-Ab, II-Ae, II-Ah, II-Aj], [II-Aa, II-Aa, II-Ab, II-Ae, II-Ah, II-Ak],[II-Aa, II-Aa, II-Ab, II-Ae, II-Ah, II-Al], [II-Aa, II-Aa, II-Ab, II-Ae,II-Al, II-Aj], [II-Aa, II-Aa, II-Ab, II-Ae, II-Al, II-Ak], [II-Aa,II-Aa, II-Ab, II-Ae, II-Al, II-Al], [II-Aa, II-Aa, II-Ab, II-Af, II-Ah,II-Aj], [II-Aa, II-Aa, II-Ab, II-Af, II-Ah, II-Ak], [II-Aa, II-Aa,II-Ab, II-Af, II-Ah, II-Al], [II-Aa, II-Aa, II-Ab, II-Af, II-Al, II-Aj],[II-Aa, II-Aa, II-Ab, II-Af, II-Al, II-Ak], [II-Aa, II-Aa, II-Ab, II-Af,II-Al, II-Al], [II-Aa, II-Aa, II-Ab, II-Ag, II-Ah, II-Aj], [II-Aa,II-Aa, II-Ab, II-Ag, II-Ah, II-Ak], [II-Aa, II-Aa, II-Ab, II-Ag, II-Ah,II-Al], [II-Aa, II-Aa, II-Ab, II-Ag, II-Al, II-Ak], [II-Aa, II-Aa,II-Ab, II-Ag, II-Aj, II-Al], [II-Aa, II-Aa, II-Ac, II-Ae, II-Ah, II-Aj],[II-Aa, II-Aa, II-Ac, II-Ae, II-Ah, II-Ak], [II-Aa, II-Aa, II-Ac, II-Ae,II-Ah, II-Al], [II-Aa, II-Aa, II-Ac, II-Ae, II-Ai, II-Aj], [II-Aa,II-Aa, II-Ac, II-Ae, II-Al, II-Ak], [II-Aa, II-Aa, II-Ac, II-Ae, II-Ai,II-Al], [II-Aa, II-Aa, II-Ac, II-Af, II-Ah, II-Aj], [II-Aa, II-Aa,II-Ac, II-Af, II-Ah, II-Ak], [II-Aa, II-Aa, II-Ac, II-Af, II-Ah, II-Al],[II-Aa, II-Aa, II-Ac, II-Af, II-Aj, II-Aj], [II-Aa, II-Aa, II-Ac, II-Af,II-Aj, II-Ak], [II-Aa, II-Aa, II-Ac, II-Af, II-Aj, II-Al], [II-Aa,II-Aa, II-Ac, II-Ag, II-Ah, II-Aj], [II-Aa, II-Aa, II-Ac, II-Ag, II-Ah,II-Ak], [II-Aa, II-Aa, II-Ac, II-Ag, II-Ah, II-Al], [II-Aa, II-Aa,II-Ac, II-Ag, II-Al, II-Aj], [II-Aa, II-Aa, II-Ac, II-Ag, II-Ai, II-Ak],[II-Aa, II-Aa, II-Ac, II-Ag, II-Al, II-Al], [II-Aa, II-Aa, II-Ad, II-Ae,II-Ah, II-Aj], [II-Aa, II-Aa, II-Ad, II-Ae, II-Ah, II-Ak], [II-Aa,II-Aa, II-Ad, II-Ae, II-Ah, II-Al], [II-Aa, II-Aa, II-Ad, II-Ae, II-Al,II-Aj], [II-Aa, II-Aa, II-Ad, II-Ae, II-Al, II-Ak], [II-Aa, II-Aa,II-Ad, II-Ae, II-Al, II-Al], [II-Aa, II-Aa, II-Ad, II-Af, II-Ah, II-Aj],[II-Aa, II-Aa, II-Ad, II-AF, II-Ah, II-Ak], [II-Aa, II-Aa, II-Ad, II-Af,II-Ah, II-Al], [II-Aa, II-Aa, II-Ad, II-Af, II-Aj, II-Aj], [II-Aa,II-Aa, II-Ad, II-Af, II-Aj, II-Ak], [II-Aa, II-Aa, II-Ad, II-Af, II-Aj,II-Al], [II-Aa, II-Aa, II-Ad, II-Ag, II-Ah, II-Aj], [II-Aa, II-Aa,II-Ad, II-Ag, II-Ah, II-Ak], [II-Aa, II-Aa, II-Ad, II-Ag, II-Ah, II-Al],[II-Aa, II-Aa, II-Ad, II-Ag, II-Ai, II-Aj], [II-Aa, II-Aa, II-Ad, II-Ag,II-Al, II-Ak], [II-Aa, II-Aa, II-Ad, II-Ag, II-Al, II-Al], [II-Aa,II-Aa, II-Ad, II-Ag, II-Al, II-Al].

In the present specification, the term “platelet production modifier”means pharmaceutical composition for hemopathy accompanied with theunusual number of platelet. For example the hemopathy isthrombocytopenia (thrombocytopenia after bone marrow transplantation,chemotherapy-induced thrombocytopenia, Aplastic anemia, myelodysplasiasyndrome, acquired thrombopenia such as idiopathic thrombopoietinicpurpura, congenital amegakaryocytic thrombocytopenia such asthrombopoietin deficiency), and the like. For example this medicine canbe used as treating agent in the case of decreasing number of plateletby administrating antitumor agent, or as protecting agent in the case ofexpecting the decrease of number of platelet by administrating antitumoragent.

In the present specification, the term “modifying a platelet production”means 1) increasing a number of platelet decreased by administratingantitumor agent and the like. 2) maintaining a number of platelet whichmay be decreased by administrating antitumor agent and the like. 3)reducing the ratio of the platelet number of decrease caused byadministrating antitumor agent and the like.

BEST MODE FOR CARRYING OUT THE INVENTION

Compounds (I) of the invention can be synthesized by the followingmethods A to B and the similar process.

wherein R⁶, R⁷, R⁸, and R⁹ are as defined above mentioned; R^(L) andR^(M) are a protecting group; X¹ is a group represented by the formula(IX), M is alkali metal.

wherein R¹, R², R³, R⁴, and R⁵ are as defined above mentioned.

(Step 1)

This step is a process of preparing the compound (V) by protecting of acarboxyl group of 4-formylbenzoic acid derivatives (IV) by R^(L). Instep 3 combination of R^(L) and R^(M) is important in order to removeselectively protecting groups of two carboxylic acid. In the case ofR^(L) is a protecting group such as methyl and ethyl, which can beremoved by basic condition, it is necessary that a protecting group ofR^(M) can be removed by another condition except basic condition.Examples of R^(M) are allyl (removed by palladium (0) complex),tert-butyl, p-methyloxybenzyl, triphenylmethyl, diphenylmethyl (removedby acidic condition), trimethylsilylethyl, trimethylsilylethoxymethyl,tert-butyldimethylsilyl (removed by fluoride ion) and the like.

Esterification condition can be used the method of reacting withconsiderable halocompound in the presence of suitable base. And it canbe synthesized by condensation reaction using an alcohol derivative asstarting material.

(Step 2)

This step is a process of preparing the compound (VI) by converting analdehyde group of the compound (V) to olefin. For examples, the olefincan be synthesized by the reaction using phosphineylide such as Wittigreaction, Horner-Emmons reaction, or by dehydrated condensation reactionsuch as Knoevenagel reaction.

(Step 3)

This step is a process of preparing the compound (VII) removing theprotecting group R^(L) of the compound (VI). The removal of protectinggroup R^(L) is carried out under suitable reaction condition asdescribed in Protective Groups in Organic Synthesis, Theodora W Green(John Wiley & Sons).

(Step 4)

This step is a process of preparing amide the compound (VIII) or thecompound (I-A wherein R^(M) is C1-C4 alkyl) from the compound (VII) andan amine derivative (X¹—NH₂) by the method such as activeesterification, acid chloride, mixed acid anhydride. This step isreacted in the solvent such as tetrahydrofuran, dioxane,dichloromethane, toluene, benzene. At active esterification method itcan be carried out by using 1-hydroxybenzotriazole, hydroxysuccinimide,dimethylaminopyridine, and the like and dicyclohexylcarbodiimide,1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride salt, andthe like as condensation reagent. At acid halide method it can becarried out by converting free carboxylic acid which is reacted withthionyl chloride or oxalyl chloride to acid chloride. At mixed acidanhydride method it can be carried out by converting carboxylic acidwhich is reacted with ethylchloroformate, isobutylchloroformate or thelike to mixed acid anhydride. Triethylamine, pyridine or the like areused as base in these reaction according to be necessary.

(Step 5)

This step is a process of preparing the compound (I-B) by removing aprotecting group R^(M) of the compound (VIII) or the compound (I-A). Theprotecting group R^(M) is removed under suitable reaction condition byusing the method as described in Protective Groups in Organic Synthesis,Theodora W Green (John Wiley & Sons).

(Step 6)

This step is a process of preparing the compound (I-A) by alkylating thecompound (I-B). This step is reacted in the solvent such astetrahydrofuran, dioxane, dichloromethane, toluene,N,N-dimethylformamide. At alkylation method it can be carried out bycondensation with C1-C6 alkyl halide in the presence of base such aspotassium carbonate, sodium hydride. At acid chloride method it can becarried out by converting free carboxylic acid which is reacted withthionyl chloride or oxalyl chloride to acid chloride, and then wasreacted with C1-C6 alcohol. Triethylamine, pyridine or the like are usedas base in these reaction according to be necessary.

(Step 7)

This step is a process of preparing the compound (I-C) by treating thecompound (I-B) with alkali metal such as sodium, potassium or alkalimetal hydroxide. This step is reacted in the solvent such astetrahydrofuran, dioxane, dichloromethane, toluene,N,N-dimethylformamide, alcohol such as methanol, ethanol, and the likein the presence of base such as alkali metal such as sodium, potassiumor alkali metal hydroxide.

(Method B)

This method is another method for preparing the compound (VIII) or thecompound (I-A) as described method A.

wherein R⁶, R⁷, R⁸, R^(M), and X¹ are as defined above mentioned.

(Step 1)

This step is a process of preparing the compound (A) in a manner similarto Step 4 of Method A.

(Step 2)

This step is a process of preparing the compound (VIII) or the compound(I-A) by converting an aldehyde group of the compound (X) to olefin in amanner similar to Step 2 of Method A.

(Method C)

This method is another method for preparing the compound (VIII) or thecompound (I-A) as described method A.

wherein R⁶, R⁷, R⁸, R^(M), and X¹ are as defined above mentioned.

(Step 1)

This step is a process of preparing the compound (XII) by converting analdehyde group of the compound (XI) to olefin group in a manner similarto Step 2 of Method A.

(Step 2)

his step is a process of preparing the compound (VIII) or the compound(I-A) by substituting a bromo group of the compound (XII). At this stepit can be carried out by adding carbon monoxide to a DMF solution of thecompound (XII) and X¹NH₂ in the presence ofdichlorobistriphenylphosphinepalladium and base such as triethylamine.The reaction temperature is used 20° C. to 120° C., preferably 50° C. to100° C. The reaction time is used 1 h to 48 h, preferably 4 h to 24 h.

The term “solvate” includes, for example, solvates with organicsolvents, hydrates, and the like.

The term “compound of the present invention” herein used includes apharmaceutically acceptable salt or solvate thereof. The salt isexemplified by a salt with alkali metals (e.g., lithium, sodium,potassium, and the like), alkaline earth metals (e.g., magnesium,calcium, and the like), ammonium, organic bases, amino acids, mineralacids (e.g., hydrochloric acid, hydrobromic acid, phosphoric acid,sulfuric acid, and the like), or organic acids (e.g., acetic acid,citric acid, maleic acid, fumaric acid, benzenesulfonic acid,p-toluenesulfonic acid, and the like). These salts can be formed by theusual method. These hydrates can coordinate with any water moleculeswhen hydrates are formed.

Prodrug is a derivative of the compound having a group which can bedecomposed chemically or metabolically, and such prodrug is a compoundaccording to the present invention which becomes pharmaceutically activeby means of solvolysis or by placing the compound in vivo under aphysiological condition. The method of both selection and manufacture ofappropriate prodrug derivatives is described in, for example. Design ofProdrugs, Elsevier, Amsterdam, 1985). For instance, prodrugs such as anester derivative which is prepared by reacting a basal acid compoundwith a suitable alcohol, or an amide derivative which is prepared byreacting a basal acid compound with a suitable amine are exemplifiedwhen the compounds according to present invention have a carboxylicgroup. Particularly preferred esters as prodrugs are methyl ester, ethylester, n-propyl ester, isopropyl ester, n-butyl ester, isobutyl ester,tert-butyl ester, morpholinoethyl ester, and N,N-diethylglycolamidoester, and the like. For instance, when the compounds according topresent invention have a hydroxy group, prodrugs such as an acyloxyderivative which is prepared by reacting with a suitable acyl halide ora suitable acid anhydride. Particularly preferred acyloxy derivatives asprodrugs —OCOC2H₅, —OCO(t-Bu), —OCOC₁₅H₃₁, —OCO(m-COONa-Ph),—COCH₂CH₂COONa, —OCOCH(NH₂)CH₃, —OCOCH₂N(CH₃)₂, and the like. Forinstance, when the compounds according to present invention have anamino group, prodrugs such as an amide derivative which is prepared byreacting with a suitable acid halide or a suitable acid anhydride.Particularly preferred amide as prodrugs are —NHCO(CH₂)₂₀CH₃,—NHCOCH(NH₂)CH₃, and the like.

The compound of the present invention is not restricted to anyparticular isomers but includes all possible isomers and racemicmodifications.

The present invention compounds show excellent thrombopoietin receptoragonism as described in examples mentioned later, and may be used as apharmaceutical composition (platelet production modifier) for hemopathyaccompanied with the unusual number of platelet, for examplethrombocytopenia (e.g., thrombocytopenia after bone marrowtransplantation, chemotherapy-induced thrombocytopenia, Aplastic anemia,myelodysplastic syndrome, acquired thrombocytopenia such as idiopathicthrombocytopenic purpura, congenital amegakaryocytic thrombocytopeniasuch as thrombopoietin deficiency), and the like. And the presentcompound may be used as treating and/or preventing agent for the unusualnumber of platelet accompanied with administering antitumor agent.

When the compound of the present invention is administered to a personfor the treatment of the above diseases, it can be administered orallyas powder, granules, tablets, capsules, pilulae, and liquid medicines,or parenterally as injections, suppositories, percutaneous formulations,insufflation, or the like. An effective dose of the compound isformulated by being mixed with appropriate medicinal admixtures such asexcipient, binder, penetrant, disintegrators, lubricant, and the like ifnecessary Parenteral injections are prepared by sterilizing the compoundtogether with an appropriate carrier.

The dosage varies with the conditions of the patients, administrationroute, their age, and body weight. In the case of oral administration,the dosage can generally be between 0.1 to 100 mg/kg/day, and preferably1 to 20 mg/kg/day for adult.

The following examples are provided to further illustrate the presentinvention and are not to be constructed as limiting the scope thereof.

Abbreviations described below are used in the following examples.

Me: methylEt: ethyln-Bu: n-butylPh: phenylTf: trifluoromethanesulfonyl

DMF: N,N-dimethylformamide

THF: tetrahydrofuran

EXAMPLES Example 1 Synthesis of Compound (A1)

1) Synthesis of 4-bromo-2,6-difluorobenzaldehyde (2)

To a THF (250 mL) solution of diisopropylamine (53 mL) was added 2.44 Mhexane solution of butyl lithium at −78° C., and the reaction mixturewas stirred for 30 minute. To the reaction mixture was added a THFsolution of 3,5-difluorobromobenzene (1) (36 g), and then the reactionmixture was stirred for 1 h. To the reaction mixture was added DMF 146mL, and the reaction mixture was stirred for additional 1 h. To thereaction mixture was added a saturated ammonium chloride aqueoussolution, and the reaction mixture was extracted with ethyl acetate. Theorganic layer was washed with water, and brine, dried over magnesiumsulfate, and evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=20:1) to obtain the compound (2)23.2 g.

¹H-NMR(CDCl₃) 10.29 (s, 1H), 7.19-7.25 (m, 2H).

2) Synthesis of ethyl 3-(4-bromo-2,6-difluorophenyl)-2-methylacrylate(3)

To a THF (100 mL) solution of triethyl-2-phosphonopropionic acid (33.8mL) was added sodium hydride (8.4 g) under ice-cooling. After thereaction mixture was stirred for 1 h, to the reaction mixture was addeda THF solution of 4-bromo-2,6-difluorobenzaldehyde (2) (23.2 g) dropwiseunder ice-cooling. After the reaction mixture was stirred underice-cooling for 2 h, to the reaction mixture were added ice-water, 2Nhydrochloric acid, and the reaction mixture was extracted with ethylacetate. The organic layer was washed with water, and brine, dried overmagnesium sulfate, and evaporated. The obtained residue was purified bycolumn chromatography (hexane:ethyl acetate=15:1) to obtain the compound(3) 32.08 g.

1H-NMR(CDCl₃) 7.32 (d, 1H, J=1.5 Hz), 7.11-7.17 (m, 2H), 4-28 (q, 2H,J=7.2 Hz), 1.86 (d, 3H, J=1.5 Hz), 1.35 (t, 3H, J=7.2 Hz).

3) Synthesis of 5-(3-methyloxyhexyn-1-yl)tetralone (5)

To a DMF (100 mL) solution of 5-hydroxytetralonetrifluoromethanesulfonic acid ester (4) (13.5 g), 3-methyloxy-1-hexane(10.3 g), dichlorobistriphenylphosphinepalladium (0.9 g), and copperiodide (0.5 g) was added triethylamine (10 mL), and then the reactionmixture was stirred at 80° C. for 64 h. To the reaction mixture wereadded water, and the reaction mixture was extracted with ethyl acetate.The organic layer was washed with water, and brine, dried over magnesiumsulfate, and evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=4:1) to obtain the compound (5) 11g.

¹H-NMR(CDCl₃) 8.01 (d, 1H, J=7.8 Hz), 7.62 (dd, 1H, J=7.4 Hz, 1.4 Hz),7.27 (t, 1H, J=7.7 Hz), 4.23 (t, 1H, J=6.6 Hz), 3.50 (s, 3H), 3.11 (t,2H, J=6.1 Hz), 2.64-2.69 (m, 2H), 2.14-2.21 (m, 2H), 1.77-1.84 (m, 2H),1.52-1.60 (m, 2H), 0.99 (t, 3H, J=7.4 Hz).

4) Synthesis of 5-(3-methyloxyhexyl)tetralone (6)

To a THF (60 mL) solution of 5-(3-methyloxyhexyn-1-yl)tetralone (5) (11g) was added 10% palladium-carbon (0.9 g), and the reaction mixture wasstirred under a hydrogen gas atmosphere for 5 h. The reaction mixturefiltered off, and the filtrate was evaporated. The obtained residue waspurified by column chromatography (hexane ethyl acetate=9:1) to obtainthe compound (6) 9.0 g.

¹H-NMR(CDCl₃) 7.94 (dd, 1H, J=7.8 Hz, 1.4 Hz), 7.36 (dd, 1H, J=7.4 Hz,1.4 Hz), 7.25 (t, 1H, J=7.7 Hz), 3.37 (s, 3H), 3.23-3.24 (m, 1H),2.91-2.96 (m, 2H), 2.63-2.83 (m, 4H), 2.05-2.17 (m, 2H), 1.71-1.77 (m,2H), 1.26-1.59 (m, 4H), 0.94 (t, 3H, J=7.2 Hz).

5) Synthesis n of4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylamine (7)

To a 10% methanol-chloroform (60 mL) solution of5-(3-methyloxyhexyl)tetralone (6) (9.0 g) was added bromine (5.5 g), andthe reaction mixture was stirred for 1 h. After the solvent wasevaporated, the residue was dissolved in ethanol (60 mL), and to theresidue was added thiourea (2.65 g). After the mixture was heated atreflux for 7 h, the reaction solvent was evaporated. To the residue wasadded a saturated sodium hydrogen carbonate aqueous solution, and themixture was extracted with ethyl acetate. The organic layer was driedover magnesium sulfate, and evaporated. The obtained residue waspurified by column chromatography (hexane:ethyl acetate=4:1) to obtainthe compound (7) 4.6 g.

¹H-NMR(CDCl₃) 7.59 (d, 1H, J=7.5 Hz), 7.17 (t, 1H, J=7.7 Hz), 7.05 (d,1H, J=7.7 Hz), 4.93 (bs, 2H), 3.36 (s, 3H), 3.21 (t, 1H, J=5.8 Hz),2.99-3.05 (m, 2H), 2.63-2.87 (m, 4H), 1.68-1.76 (m, 4H), 1.35-1.56 (m,4H), 0.93 (t, 3H, J=7.2 Hz).

6) Synthesis of ethyl3-{2,6-difluoro-4-[4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylate(8)

To a DMF (25 mL) solution of4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylamine (7) (4.5g), 3-(4-bromo-2,6-difluorophenyl)-2-methylacrylic acid ethyl ester (3)(4.35 g), and dichlorobistriphenylphosphinepalladium (0.8 g) was addedtriethylamine (10 mL), and the reaction mixture was stirred under carbonmonoxide atmosphere at 85° C. for 16 h. To the reaction mixture wasadded water, and the reaction mixture was extracted with ethyl acetate.The organic layer was washed with water, and brine, dried over magnesiumsulfate, and evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=4:1) to obtain the compound (8) 7.1g.

¹H-NMR(CDCl₃) 7.36-7.38 (m, 3H), 7.25 (bs, 1H), 7.00 (d, 2H, J=2.3 Hz),4.29 (q, 2H, J=7.2 Hz), 3.38 (s, 3H), 3.22 (t, 1H, J=5.5 Hz), 3.01-3.05(m, 4H), 2.60-2.80 (m, 2H), 1.80 (s, 3H), 1.67-1.75 (m, 2H), 1.24-1.60(m, 7H), 0.94 (t, 3H, J=7.2 Hz).

7) Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A1)

A mixture of THF (40 mL), methanol (40 mL), and 2N sodium hydroxideaqueous solution (40 mL) of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid ethyl ester (8) (7.0 g), was stirred at room temperature for 3 h.The reaction mixture was acidified with hydrochloric acid, and extractedwith ethyl acetate. The organic layer was washed with water, and brine,dried over magnesium sulfate, and evaporated. The residue wasrecrystallized from ethyl acetate to obtain the compound (A1) 5.5 g.

¹H-NMR(DMSO-d₆) 12.93 (bs, 2H), 7.95 (d, 2H, J=8.3 Hz), 7.64 (d, 1H,J=7.5 Hz), 7.33 (s, 3H), 7.09 (d, 1H, J=6.7 Hz), 3.27 (s, 3H), 3.21 (t,1H, J=6.3 Hz), 2.99 (s, 4H), 2.60-2.80 (m, 2H), 1.80 (d, 3H, J=1.6 Hz),1.64-1.66 (m, 2H), 1.45-1.47 (m, 2H), 1.31-1.33 (m, 2H), 0.89 (t, 3H,J=7.0 Hz).

Example 2 Synthesis of Compound (A1307)

1) Synthesis of tert-butyl 3-(2-isopropylphenoxy)propionate (10)

2-Isopropylphenol (6 g) was dissolved in acrylic acid tert-butyl ester(6.2 g), and to the mixture was added potassium tert-butyloxide (0.3 g).The reaction mixture was stirred at 130° C. for 6 h. To the reactionmixture was added water, the reaction mixture extracted with ethylacetate. The organic layer was washed with brine, dried over magnesiumsulfate, and evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=9:1) to obtain the compound (10)4.3 g.

1H-NMR(CDCl3) 7.20 (dd, 1H, J=7.5, 1.7 Hz), 7.14 (dt, 1H, J=7.5, 1.7Hz), 6.92 (dd, 1H, J=7.5, 1.7 Hz), 6.86 (dt, 1H, J=7.5, 1.7 Hz), 4.21(t, 2H, J=6.3 Hz), 3.30 (sext, 1H, J=7.0 Hz), 2.72 (t, 2H, J=6.3 Hz),1.45 (s, 9H), 1.15 (d, 6H, J=7.0 Hz).

2) Synthesis of 3-(2-isopropylphenoxy)propionic acid (11)

3-(2-Isopropylphenoxy)propionic acid tert-butyl ester (10) (4.3 g) wasdissolved in dichloromethane (40 mL), and to the mixture was addedtrifluoroacetic acid (4 mL). The reaction mixture was stirred at roomtemperature for 3 h, and evaporated. The obtained residue was purifiedby column chromatography (hexane:ethyl acetate=4:1) to obtain thecompound (II) 3.14 g.

1H-NMR(CDCl3) 7.23 (dd, 1H, J=7.5, 1.7 Hz), 7.17 (dt, 1H, J=7.5, 1.7Hz), 6.95 (dd, 1H, J=7.5, 1.7 Hz), 6.89 (dt, 1H, J=7.5, 1.7 Hz), 4.26(t, 2H, J=6.3 Hz), 3.30 (sext, 1H, J=7.0 Hz), 2.78 (t, 2H, J=6.3 Hz),1.19 (d, 6H, J=7.0 Hz).

3) Synthesis of 8-isopropylchroman-4-one (12)

3-(2-Isopropylphenoxy)propionic acid (11) was dissolved indichloromethane (30 mL), and to the mixture were added oxalyl chloride(2.1 g) and DMF (5 mL) under ice-cooling. The reaction mixture wasstirred for 30 minutes and cooled at −20° C. To the reaction mixture wasadded aluminum chloride (4 g), and the reaction mixture was stirred at−20° C. for 2 h. To the reaction mixture was added 2N hydrochloric acid,and the reaction mixture was extracted with dichloromethane. The organiclayer was washed with brine, dried over magnesium sulfate, andevaporated. The obtained residue was purified by column chromatography(hexane:ethyl acetate=4:1) to obtain the compound (12) 2.3 g.

1H-NMR(CDCl3) 7.73 (d, 1H, J=7.5 Hz), 7.37 (d, 1H, J=7.5 Hz), 6.93 (t,1H, J=7.5 Hz), 4.56 (t, 2H, J=6.3 Hz), 3.25 (sext, 1H, J=7.0 Hz), 2.78(t, 2H, J=6.3 Hz), 1.24 (d, 6H, J=7.0 Hz).

4) Synthesis of 6-isopropyl-4H-chromeno[4,3-d]thiazol-2-ylamine (13)

8-Isopropylchroman-4-one (12) (2.3 g) was dissolved with 10%methanol-chloroform (20 mL), and to the mixture was added bromine (1.93g). After the reaction mixture was stirred for 1 h, and evaporated. Theresidue was dissolved in ethanol (30 mL), and to the reaction mixturewas added thiourea (0.92 g). The reaction mixture was heated at reflux,and evaporated. The residue was extracted with ethyl acetate, and asaturated sodium hydrogencarbonate aqueous solution, and the organiclayer was dried over magnesium sulfate, and evaporated. The residue waspurified by column chromatography (hexane ethyl acetate=4:1) to obtainthe compound (13) 0.7 g.

1H-NMR(CDCl3) 7.43 (d, 1H, J=7.5 Hz), 7.10 (d, 1H, J=7.5 Hz), 6.95 (t,1H, J=7.5 Hz), 5.29 (s, 2H), 5.20 (bs, 2H), 3.25 (sext, 1H, J=7.0 Hz),1.24 (d, 6H, J=7.0 Hz).

5)(E)-3-[2,6-difluoro-4-(6-isopropyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid ethyl ester(14)

6-Isopropyl-4H-chromeno[4,3-d]thiazol-2-ylamine (13) (360 mg),(Z)-3-(4-bromo-2,6-difluorophenyl)-2-methylacrylic acid ethyl ester (460mg), and dichlorobistriphenylphosphinepalladium (150 mg) were dissolvedin DMF (6 mL). To the mixture was poured triethylamine (0.84 mL), andthe reaction mixture was stirred under carbon monoxide atmosphere at 85°C. for 16 h. The reaction mixture was added into water, and extractedwith ethyl acetate. The organic layer was washed with water, and brine,and dried over magnesium sulfate, and evaporated. The residue waspurified by column chromatography (hexane:ethyl acetate=4:1) to obtainthe compound (14) 620 mg.

1H-NMR(CDCl3) 7.44 (s, 1H), 7.42 (s, 1H), 7.28-7.33 (m, 1H), 7.10 (d,1H, J=7.6 Hz), 6.85 (t, 1H, J=7.6 Hz), 5.49 (s, 2H), 4.27 (q, 2H, J=7.0Hz), 3-25 (sext, 1H, J=7.0 Hz), 1.79 (s, 3H), 1.25 (t, 3H, J=7.0 Hz),1.20 (d, 6H, J=7.0 Hz).

6)(E)-3-[2,6-difluoro-4-(6-isopropyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1309)

(E)-3-[2,6-difluoro-4-(6-isopropyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid ethyl ester (620 mg) was dissolved in THF (2 mL), methanol (2 ml),and 2N sodium hydroxide aqueous solution (2 mL), and the reactionmixture was stirred at room temperature for 3 h. The reaction mixturewas acidified with hydrochloric acid and extracted with ethyl acetate.The organic layer was washed with water, and brine, dried over magnesiumsulfate, and evaporated. The residue was recrystallized from ethylacetate to obtain the compound (A1309) 460 mg.

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.98 (s, 1H), 7.97 (s, 1H), 7.48 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.11 (d, 1H, J=7.6 Hz), 7.01 (t, 1H, J=7.6 Hz),5.49 (s, 2H), 3.20-3.30 (m, 1H), 1.79 (s, 3H), 1.04 (d, 6H, J=6.0 Hz).A2-A12, A339, A341, A346, A347, A349, A351, A401, A423, A430, A440,A450, A500, A601, A928, A930, A936, A937, A939, A941, A944, A954, A993,A1003, A1016, A1018, A1033, A1123, A1295-A1308, and A1310-A1332 weresynthesized by similar method described above.

Example 3 Synthesis of3-[2,6-difluoro-4-(4,5-dihydro-6-pentylnaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A2)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.91-7.98 (m, 2H), 7.62-7.65 (m, 1H),7.33 (s, 1H), 7.18-7.23 (m, 1H), 7.06-7.10 (m, 1H), 2.97 (s, 4H), 2.63(t, 2H, J=7.6 Hz), 1.80 (s, 3H), 1.52 (t, 2H, J=6.9 Hz), 1.32-1.35 (m,4H), 0.88 (t, 3H, J=6.0 Hz).

Example 4 Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3,3-dimethylbutyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A3)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.92 (d, 2H, J=8.1 Hz), 7.60 (d, 1H,J=7.5 Hz), 7.30 (s, 1H), 7.17 (d, 1H, J=7.5 Hz), 7.03-7.06 (m, 1H), 2.94(s, 4H), 2.53-2.59 (m, 2H), 1.77 (s, 3H), 1.31-1.37 (m, 2H), 0.91 (s,9H).

Example 5 Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-methyloxy-4,4-dimethylpentyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A4)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.95 (d, 2H, J=7.6 Hz), 7.63 (d, 1H,J=7.6 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H,J=7.6 Hz), 3.33 (s, 3H), 3.21-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.70(m, 2H), 1.80 (d, 3H, J=1.3 Hz), 1.70-1.80 (m, 2H), 0.88 (s, 9H).

Example 6 Synthesis of3-{4-[6-(3-n-butyloxypropyl)-4,5-dihydronaphto[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A5)

1H-NMR(DMSO-d6) 12.94 (bs, 1H), 7.94 (d, 2H, J=7.6 Hz), 7.64 (d, 1H,J=7.6 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.05 (d, 1H,J=7.6 Hz), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.65 (t, 2H, J=7.6 Hz),1.88 (d, 3H, J=1.3 Hz), 1.70-1.80 (m, 2H), 1.45-1.53 (m, 2H), 1.31-1.40(m, 2H), 0.89 (t, 3H, J=7.4 Hz).

Example 7 Synthesis of3-(2,6-difluoro-4-{4,5-dihydro-6-[3-(2,2-dimethylpropyloxy)propyl]naphtho[1,2-d]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (A6)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.95 (d, 2H, J=7.6 Hz), 7.65 (d, 1H,J=7.6 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H,J=7.6 Hz), 3.40 (t, 2H, J=6.4 Hz), 3.05 (s, 2H), 2.95-2.99 (m, 4H), 2.71(t, 2H, J=7.4 Hz), 1.84 (d, 3H, J=1.3 Hz), 1.70-1.80 (m, 2H), 0.91 (s,9H).

Example 8 Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-isopropyloxypropyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A7)

1H-NMR(DMSO-d6) 12.94 (bs, 1H), 7.95 (d, 2H, J=7.3 Hz), 7.65 (d, 1H,J=7.3 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.3 Hz), 7.09 (d, 1H,J=7.3 Hz), 3.53 (hept, 1H, J=6.1 Hz), 3.40 (t, 2H, J=6.4 Hz), 2.95-2.99(m, 4H), 2.69 (t, 2H, J=7.0 Hz), 1.84 (d, 3H, J=1.3 Hz), 1.75-1.80 (m,2H), 1.11 (d, 6H, J=6.1 Hz).

Example 9 Synthesis of3-{2,6-difluoro-4,5-dihydro-4-[6-(3-ethyloxypropyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A8)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.95 (d, 2H, J=7.6 Hz), 7.64 (d, 1H,J=7.6 Hz), 7.34 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H,J=7.6 Hz), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.71 (t, 2H, J=7.0 Hz),1.80 (d, 3H, J=1.3 Hz), 1.70-1.80 (m, 2H), 1.12 (t, 3H, J=7.4 Hz).

Example 10 Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-n-propyloxypropyl)naphto[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A9)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.95 (d, 2H, J=7.6 Hz), 7.65 (d, 1H,J=7.6 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H,J=7.6 Hz), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.70 (t, 2H, J=7.0 Hz),1.80 (d, 3H, J=1.3 Hz), 1.70-1.80 (m, 2H), 1.45-1.53 (m, 2H), 0.89 (t,3H, J=7.4 Hz).

Example 11 Synthesis of3-{2,6-dichloro-4-[4,5-dihydro-6-(3-ethyloxypropyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A10)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.71 (t, 2H, J=7.0 Hz), 1.75-1.80(m, 2H), 1.70 (d, 3H, J=1.3 Hz), 1.12 (t, 3H, J=7.0 Hz).

Example 12 Synthesis of3-{4-[6-(3-n-butyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-dichlorophenyl}-2-methylacrylicacid (A11)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 8.27 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.70 (t, 2H, J=7.0 Hz), 1.75-1.80(m, 2H), 1.70 (d, 3H, J=1.3 Hz), 1.52-1.58 (m, 2H), 1.31-1.40 (m, 2H),0.89 (t, 3H, J=7.0 Hz).

Example 13 Synthesis of3-{2,6-difluoro-4-[4,5-dihydro-6-(3-methyloxyhexyl)naphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A12)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.27 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.24 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.33 (s, 3H), 3.21-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.70 (m, 2H),1.70 (d, 3H, J=1.3 Hz), 1.65-1.70 (m, 2H), 1.52-1.58 (m, 2H), 1.31-1.40(m, 2H), 0.89 (t, 3H, J=7.0 Hz).

Example 14 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-methyloxypentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A339)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.27 (s, 3H), 3.10-3.16 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.80 (m, 2H),1.80 (s, 3H), 1.60-1.70 (m, 2H), 1.45-1.60 (m, 2H), 0.86 (t, 3H, J=7.6Hz).

Example 15 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-methyloxyheptyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A341)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.25 (s, 3H), 3.14-3.22 (m, 1H), 2.95-2.99 (m, 4H), 2.50-2.65 (m, 2H),1.79 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.22-1.34 (m, 4H),0.90-094 (m, 3H).

Example 16 Synthesis of(E)-3-{4-[6-(3-ethyloxypentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A346)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.18 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.45 (q, 2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.60-2.80(m, 2H), 1.79 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.13 (t,3H, J=7.0 Hz), 0.86 (t, 3H, J=7.6 Hz).

Example 17 Synthesis of(E)-3-{4-[6-(3-ethyloxyhexyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A347)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.20 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.45 (q, 2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.60-2.80(m, 2H), 1.79 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.30-1.40(m, 2H), 1.13 (t, 3H, J=7.0 Hz), 0.86 (t, 3H, J=7.6 Hz).

Example 18 Synthesis of(E)-3-{4-[6-(3-ethyloxyheptyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A349)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.20 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.48 (q, 2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H,), 2.60-2.80(m, 2H), 1.79 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.30-1.40(m, 4H), 1.13 (t, 3H, J=7.0 Hz), 0.86-0.89 (m, 3H).

Example 19 Synthesis of(E)-3-{4-[6-(3-ethyloxy-4,4-dimethylpentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A351)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.23 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.50-3.65 (m, 2H), 2.95-2.99 (m, 4H), 2.80-2.90 (m, 2H), 2.59-2.65 (m,1H), 1.80 (s, 3H), 1.60-1.70 (m, 1H), 1.45-1.5 (m, 1H), 1.17 (t, 3H,J=7.0 Hz), 0.90 (s, 9H).

Example 20 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-pentyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A401)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.36 (t, 2H, J=6.4 Hz), 3.28 (t, 2H, J=7.0 Hz), 2.95-2.99 (m, 4H), 2.74(t, 2H, J=7.0 Hz), 1.78 (s, 3H), 1.69-1.75 (m, 2H), 1.48-1.55 (m, 2H),1.22-1.34 (m, 4H), 0.90-0.94 (m, 3H).

Example 21 Synthesis of(Z)-3-{2,6-difluoro-4-[6-(3-methyloxyhexyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A423)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.20 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 6.65 (s, 1H),3.7 (s, 3H), 3.22 (s, 3H), 3.14-3.22 (m, 1H), 2.95-2.99 (m, 4H),2.55-2.70 (m, 2H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.22-1.34 (m,2H), 0.90-0.94 (m, 3H).

Example 22 Synthesis of(Z)-3-{4-[6-(3-ethyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (A430)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.06 (d, 1H, J=7.6 Hz), 6.61 (s, 1H),3.71 (s, 3H), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.71 (t, 2H, J=7.0Hz), 1.70-1.80 (m, 2H), 1.13 (t, 3H, J=7.0 Hz).

Example 23 Synthesis of(Z)-3-{2,6-difluoro-4-[6-(3-propyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A440)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.92 (s, 1H), 7.89 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.06 (d, 1H, J=7.6 Hz), 6.62 (s, 1H),3.71 (s, 3H), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.71 (t, 2H, J=7.0Hz), 1.70-1.80 (m, 2H), 1.45-1.55 (m, 2H), 0.89 (t, 3H, J=7.0 Hz).

Example 24 Synthesis of(Z)-3-{2,6-difluoro-4-[6-(3-isopropyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A450)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.91 (s, 1H), 7.89 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.20 (t, 1H, J=7.6 Hz), 7.04 (d, 1H, J=7.6 Hz), 6.66 (s, 1H),3.71 (s, 3H), 3.50-3.60 (m, 1H), 3.38 (t, 2H, J=7.0 Hz), 2.95-2.99 (m,4H), 2.69 (t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H), 1.11 (d, 6H, J=6.0 Hz).

Example 25 Synthesis of(Z)-3-(4-{6-[3-(2,2-dimethylpropyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (A503)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.64 (d, 1H,J=7.6 Hz), 7.20 (t, 1H, J=7.6 Hz), 7.04 (d, 1H, J=7.6 Hz), 6.65 (s, 1H),3.71 (s, 3H), 3.40 (t, 2H, J=7.0 Hz), 3.07 (s, 2H), 2.95-2.99 (m, 4H),2.69 (t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H), 0.90 (s, 9H).

Example 26 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3,3-dimethylbutyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A601)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 8.28 (s, 2H), 7.61-7.64 (m, 1H), 7.40(d, 1H, J=1.3 Hz), 7.18-7.23 (m, 1H), 7.07-7.10 (m, 1H), 2.98 (s, 4H),2.49-2.64 (m, 2H), 1.69 (s, 3H), 1.35-1.41 (m, 2H), 0.98 (s, 9H).

Example 27 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-methyloxypentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A928)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.27 (s,3H), 3.10-3.16 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.80 (m, 2H), 1.68 (s,3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 0.86 (t, 3H, J=7.6 Hz).

Example 28 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-methyloxyheptyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A930)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.27 (s,3H), 3.14-3.22 (m, 1H), 2.95-2.99 (m, 4H), 2.55-2.65 (m, 2H), 1.68 (s,3H), 1.66-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.22-1.34 (m, 4H), 0.90-094(m, 3H).

Example 29 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-methyloxy-4,4-dimethylpentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A932)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.44 (s, 3H), 2.95-2.99 (m, 4H), 2.65-2.70 (m, 2H), 1.68 (s, 3H),1.45-1.55 (m, 2H), 0.90 (s, 9H).

Example 30 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-ethyloxypentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A936)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.45 (q,2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.80 (m, 2H),1.68 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.13 (t, 3H, J=7.0Hz), 0.86 (t, 3H, J=7.6 Hz).

Example 31 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-ethyloxyhexyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A937)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.63 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.07 (d, 1H, J=7.6 Hz), 3.47 (q,2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.80 (m, 2H),1.68 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.30-1.40 (m, 2H),1.13 (t, 3H, J=7.0 Hz), 0.86 (t, 3H, J=7.6 Hz).

Example 32 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-ethyloxyheptyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A939)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.23 (s, 2H), 7-63 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.10 (d, 1H, J=7.6 Hz), 3.47 (q,2H, J=7.0 Hz), 3.20-3.26 (m, 1H), 2.95-2.99 (m, 4H), 2.65-2.80 (m, 2H),1.68 (s, 3H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.30-1.40 (m, 4H),1.13 (t, 3H, J=7.0 Hz), 0.86-0.89 (m, 3H).

Example 33 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-ethyloxy-4,4-dimethylpentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A941)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.12 (d, 1H, J=7.6 Hz), 3.50-3.65(m, 2H), 2.95-2.99 (m, 4H), 2.80-2.90 (m, 2H), 2.59-2.65 (m, 1H), 1.68(s, 3H), 1.60-1.70 (m, 1H), 1.45-1.050 (m, 1H), 1.17 (t, 3H, J=7.0 Hz),0.90 (s, 9H).

Example 34 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-propyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A944)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.2 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H), 2.70 (t, 2H, J=7.0 Hz), 1.70-1.80(m, 2H), 1.66 (s, 3H), 1.45-1.53 (m, 2H), 0.88 (t, 3H, J=7.4 Hz).

Example 35 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-isopropyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A954)

1H-NMR(DMSO-d6) 12.9 (bs, 1H), 8.28 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.50-3.58 (m, 1H), 3.38 (t, 2H, J=7.0), 2.95-2.99 (m, 4H), 2.70 (t, 2H,J=7.0 Hz), 1.70-1.80 (m, 2H), 1.66 (s, 3H), 1.10 (d, 6H, J=6.0 Hz).

Example 36 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-pentyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A993)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.24 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.36 (t,2H, J=6.4 Hz), 3.28 (t, 2H, J=7.0 Hz), 2.95-2.99 (m, 4H), 2.70 (t, 2H,J=7.0 Hz), 1.69-1.75 (m, 2H), 1.68 (s, 3H), 1.48-1.55 (m, 2H), 1.22-1.34(m, 4H), 0.90-0.94 (m, 3H).

Example 37 Synthesis of(E)-3-(2,6-dichloro-4-{6-[3-(2,2-dimethylpropyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A 1003)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.27 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.38 (t, 2H, J=7.0 Hz), 3.07 (s, 2H), 2.95-2.99 (m, 4H), 2.70 (t, 2H,J=7.0 Hz), 1.70-1.80 (m, 2H), 1.68 (s, 3H), 0.90 (s, 9H).

Example 38 Synthesis of(Z)-3-{2,6-dichloro-4-[6-(3-methyloxyhexyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylcacid (A1016)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.23 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 6.76 (s, 1H), 3.60 (s,3H), 3.27 (s, 3H), 3.14-3.22 (m, 1H), 2.95-2.99 (m, 4H), 2.55-2.75 (m,2H), 1.60-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.22-1.34 (m, 2H), 0.90-094(m, 3H).

Example 39 Synthesis of(Z)-3-{2,6-dichloro-4-[6-(3-methyloxyheptyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A1018)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.27 (s, 2H), 7.64 (d, 1H, J=7.6 Hz),7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 6.73 (s, 1H), 3.61 (s,3H), 3.27 (s, 3H), 3.14-3.22 (m, 1H), 2.95-2.99 (m, 4H), 2.55-2.65 (m,2H), 1.62-1.69 (m, 2H), 1.45-1.55 (m, 2H), 1.22-1.34 (m, 2H), 0.90-094(m, 3H).

Example 40 Synthesis of(Z)-3-{2,6-dichloro-4-[6-(3-propyloxypropyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A1033)

1H-NMR(DMSO-d6) 12.95 (bs, 1H), 8.23 (s, 2H), 7.62 (d, 1H, J=7.6 Hz),7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 6.73 (s, 1H), 3.61 (s,3H), 3.33-3.40 (m, 4H), 2.95-2.99 (m, 4H, 2.70 (t, 2H, J=7.0 Hz),1.70-1.80 (m, 2H), 1.45-1.53 (m, 2H), 0.89 (t, 3H, J=7.0 Hz).

Example 41 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-propyloxypropyl)-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A1123)

1H-NMR(DMSO-d6) 12.9 (bs, 1H), 8.28 (s, 2H), 7.49 (d, 1H, J=7.6 Hz),7.38 (s, 1H), 7.09 (d, 1H, J=7.6 Hz), 6.97 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 3.33-3.40 (m, 4H), 2.63 (t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H), 1.68(s, 3H), 1.45-1.53 (m, 2H), 0.89 (t, 3H, J=7.4 Hz).

Example 42 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-methyloxy-3-methylbutyl)-4,5-dihydronaphto[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A 1295)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.5 Hz), 7.33 (s, 1H), 7.21 (t, 2H, J=7.5 Hz), 7.11 (d, 1H, J=7.5 Hz),3.18 (s, 3H), 2.60-2.65 (m, 2H), 1.79 (s, 3H), 1.60-1.69 (m, 2H), 1.18(s, 6H).

Example 43 Synthesis of(E)-3-(4-{6-[3-(2-ethyloxy-1-ethyloxymethylethyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A1296)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.97 (s, 1H), 7.94 (s, 1H), 7.65 (d, 1H,J=7.5 Hz), 7.33 (s, 1H), 7.21 (t, 2H, J=7.5 Hz), 7.10 (d, 1H, J=7.5 Hz),3.56-3.60 (m, 4H), 3.40-3.50 (m, 7H), 2.95-2.99 (m; 4H), 2.69 (t, 2H,J=7.3 Hz), 1.79 (s, 3H), 1.67-1.73 (m, 2H), 1.10 (t, 6H, J=7.3 Hz).

Example 44 Synthesis of(E)-3-(2,6-difluoro-4-{6-[3-(2-isopropyloxyethyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (A1297)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.97 (s, 1H), 7.94 (s, 1H), 7.65 (d, 1H,J=7.5 Hz), 7.33 (s, 1H), 7.21 (t, 2H, J=7.5 Hz), 7.11 (d, 1H, J=7.5 Hz),3.56-3.60 (m, 2H), 2.95-2.99 (m, 4H), 2.70 (t, 2H, J=7.4 Hz), 1.78 (s,3H), 1.65-1.70 (m, 2H), 1.10 (d, 6H, J=6.0 Hz).

Example 45 Synthesis of(E)-3-(2,6-difluoro-4-{6-[3-(2-ethyloxy-1-ethyloxymethylethyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (A1298)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.27 (s, 2H), 7.66 (d, 1H, J=7.6 Hz),7.39 (s, 1H), 7.20 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.56-3.60(m, 4H), 3.40-3.50 (m, 7H), 2.95-2.99 (m, 4H), 2.69 (t, 2H, J=7.2 Hz),1.65-1.78 (m, 2H), 1.69 (s, 3H), 1.02 (t, 6H, J=7.2 Hz).

Example 46 Synthesis of(E)-3-(2,6-dichloro-4-{6-[3-(2-methyloxyethyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (A 1299)

1H-NMR(DMSO-d6) 12.92 (bs, 1H,), 8.28 (s, 2H,), 7.64 (d, 1H, J=7.6 Hz),7.40 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz),3.40-3.50 (m, 6H), 3.18 (s, 3H), 2.95-2.99 (m, 4H), 2.68 (t, 2H, J=7.4Hz), 1.68-1.78 (m, 2H), 1.68 (s, 3H).

Example 47 Synthesis of(E)-3-(2,6-difluoro-4-{6-[3-(2-methyloxyethyloxy)propyl]-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (A1300)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.65 (d, 1H,J=7.6 Hz), 7.33 (d, 1H, J=1.3 Hz), 7.21 (t, 1H, J=7.6 Hz), 7.09 (d, 1H,J=7.6 Hz), 3.40-3.50 (m, 6H), 3.18 (s, 3H), 2.95-2.99 (m, 4H), 2.68 (t,2H, J=7.4 Hz), 1.80-1.88 (m, 2H), 1.78 (s, 3H).

Example 48 Synthesis of(E)-3-[2,6-difluoro-4-(6-hexyloxy-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1301)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.37 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.24 (t, 1H, J=7.6 Hz), 6.92 (d, 1H, J=7.6 Hz),4.00 (t, 2H, J=7.0 Hz), 2.95-2.99 (m, 4H), 1.80 (s, 3H), 1.70-1.80 (m,2H), 1.45-1.55 (m, 2H), 1.30-1.40 (m, 4H), 0.89-0.91 (m, 3H).

Example 49 Synthesis of(E)-3-[2,6-dichloro-4-(6-hexyloxy-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1302)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.39 (s, 1H), 7.37 (d, 1H,J=7.6 Hz), 7.24 (t, 1H, J=7.6 Hz), 6.91 (d 1H, J=7.6 Hz), 4.00 (t, 2H,J=7.0 Hz), 2.95-2.99 (m, 4H), 1.70-1.80 (m, 2H), 1.68 (s, 3H), 1.45-1.55(m, 2H), 1.30-1.40 (m, 4H), 0.89-0.91 (m, 3H).

Example 50 Synthesis of(E)-3-[2,6-dichloro-4-(6-isobutyloxy-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1303)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.39 (s, 1H), 7.37 (d, 1H,J=7.6 Hz), 7.24 (t, 1H, J=7.6 Hz), 6.89 (d, 1H, J=7.6 Hz), 3.79 (d, 2H,J=6.6 Hz), 2.95-2.99 (m, 4H), 2.05-2.15 (m, 1H), 1.68 (s, 3H), 1.02 (d,6H, J=6.0 Hz).

Example 51 Synthesis of(E)-3-[2,6-difluoro-4-(6-isobutyloxy-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1304)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.37 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.24 (t, 1H, J=7.6 Hz), 6.92 (d, 1H, J=7.6 Hz),3.79 (d, 2H, J=6.6 Hz), 2.95-2.99 (m, 4H), 2.05-2.15 (m, 1H), 1.78 (s,3H), 1.02 (d, 6H, J=6.0 Hz).

Example 52 Synthesis of(E)-3-{4-[6-(2-ethyloxyethyloxy)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A1305)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.40 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.24 (t, 1H, J=7.6 Hz), 6.95 (d, 1H, J=7.6 Hz),4.13 (t, 2H, J=5.0 Hz), 3.73 (t, 2H, J=5.0 Hz), 3.54 (q, 2H, J=7.0 Hz),2.95-2.99 (m, 4H,), 1.78 (s, 3H), 1.15 (t, 3H, J=7.0 Hz).

Example 53 Synthesis of(E)-3-{2,6-dichloro-4-[6-(2-ethyloxyethyloxy)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A1306)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.39 (s, 1H), 7.37 (d, 1H,J=7.6 Hz), 7.24 (t, 1H, J=7.6 Hz), 6.95 (d, 1H, J=7.6 Hz), 4.13 (t, 2H,J=5.0 Hz), 3.73 (t, 2H, J=5.0 Hz), 3.54 (q, 2H, J=7.0 Hz), 2.95-2.99 (m,4H), 1.68 (s, 3H), 1.14 (t, 3H, J=7.0 Hz).

Example 54 Synthesis of(E)-3-[4-(6-ethyl-4H-chromeno[4,3-d]thiazol-2-ylcabamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A1307)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.48 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.11 d, 1H, J=7.6 Hz), 6.97 (d, 1H, J=7.6 Hz),5.49 (s, 2H), 2-60 (q, 2H, J=7.0 Hz), 1.79 (s, 3H), 1.14 (t, 3H, J=7.0Hz).

Example 55 Synthesis of(E)-3-[2,6-difluoro-4-(6-propyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1308)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.49 (d, 1H,J=7-6 Hz), 7.33 (s, 1H), 7.07 (d, 1H, J=7.6 Hz), 6.97 (t, 1H, J=7.6 Hz),5.47 (s, 2H), 2.53 (t, 2H, J=7.0 Hz), 1.79 (s, 3H), 1.49-1.59 (m, 2H),0.94 (t, 3H, J=7.0 Hz).

Example 56 Synthesis of(E)-3-[2,6-dichloro-4-(6-ethyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1310)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.26 (s, 2H), 7.47 (d, 1H, J=7.6 Hz),7.38 (s, 1H), 7.09 (d 1H, J=7.6 Hz), 6.95 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 2.55 (q, 2H, J=7.0 Hz), 1.69 (s, 3H), 1.14 t, 3H, J=7.0 Hz).

Example 57 Synthesis of(E)-3-[2,6-dichloro-4-(6-propyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1311)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.27 (s, 2H), 7.47 (d, 1H, J=7.6 Hz),7.38 (s, 1H), 7.09 (d, 1H, J=7.6 Hz), 6.95 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 2.53 (t, 2H, J=7.0 Hz), 166 (s, 3H), 1.49-1.59 (m, 2H), 0.94 (t,3H, J=7.0 Hz).

Example 58 Synthesis of(E)-3-[2,6-dichloro-4-(6-isopropyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1312)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.27 (s, 2H), 7.49 (d, 1H, J=7.6 Hz),7.38 (s, 1H), 7.13 (d, 1H, J=7.6 Hz), 7.01 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 3.20-3.30 (m, 2H), 1.69 (s, 3H), 1.04 (d, 6H, J=6.0 Hz).

Example 59 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-propyloxypropyl)-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A1313)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.49 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.10 (d, 1H, J=7.6 Hz), 6.95 (t, 1H, J=7.6 Hz),5.49 (s, 2H), 3.33-3.40 (m, 4H), 2.63 (t, 2H, J=7.0 Hz), 1.80 (s, 3H),1.70-1.80 (m, 2H), 1.45-1.53 (m, 2H), 0.89 (t, 3H, J=7.4 Hz).

Example 60 Synthesis of(E)-3-[2,6-difluoro-4-(6-hexyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1314)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.49 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.10 (d, 1H, J=7.6 Hz), 6.97 (t, 1H, J=7.6 Hz),5.47 (s, 2H), 2.53 (t, 2H, J=7.0 Hz), 1.80 (s, 3H), 1.49-1.59 (m, 2H),1.25-1.36 (m, 6H), 0.94 (t, 3H, J=7.0 Hz).

Example 61 Synthesis of(E)-3-{4-[6-(3,3-dimethylbutyl)-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (A1315)

1H-NMR(DMSO-d6) 12.93 (bs, 1H), 7.96 (s, 1H), 7.94 (s, 1H), 7.4 (d, 1H,J=7.6 Hz), 7.33 (s, 1H), 7.10 (d, 1H, J=7.6 Hz), 6.97 (t, 1H, J=7.6 Hz),5.47 (s, 2H), 2.50-2.60 (m, 2H), 1.80 (s, 3H), 1.39-1.45 (m, 2H), 0.95(s, 9H).

Example 62 Synthesis of(E)-3-[2,6-dichloro-4-(6-hexyl-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1316)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.27 (s, 2H), 7.48 (d, 1H, J=7.6 Hz),7.3 (s, 1H), 7.09 (d, 1H, J=7.6 Hz), 6.97 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 2.56 (t, 211, J=7.0 Hz), 1.68 (s, 3H), 1.49-1.59 (m, 2H), 1.25-1.36(m, 6H), 0.86 (t, 3H, J=7.0 Hz).

Example 63 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3,3-dimethylbutyl)-4H-chromeno[4,3-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (A1317)

1H-NMR(DMSO-d6) 12.92 (bs, 1H), 8.28 (s, 2H), 7.50 (d, 1H, J=7.6 Hz),7.40 (s, 1H), 7.09 (d, 1H, J=7.6 Hz), 6.96 (t, 1H, J=7.6 Hz), 5.49 (s,2H), 2.50-2.60 (m, 2H), 1.68 (s, 3H), 1.39-1.45 (m, 2H), 0.95 (s, 9H).

Example 64 Synthesis of(Z)-3-{2,6-dichloro-4-[6-(3,3-dimethylbutyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (A1318)

1H-NMR(DMSO-d6) 12.90 (bs, 2H), 8.23 (s, 2H), 7.63 (d, 1H, J=7.5 Hz),7.20 (t, 1H, J=7.5 Hz), 7.08 (d, 1H, J=7.7 Hz), 6.73 (s, 1H), 3.61 (s,3H), 2.98 (s, 4H), 2.49-2.64 (m, 2H), 1.35-1.41 (m, 2H), 0.98 (s, 9H).

Example 65 Synthesis of(Z)-3-{4-[6-(3,3-dimethylbutyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (A 1319)

1H-NMR(DMSO-d6) 12.87 (bs, 2H), 7.88-7.91 (m, 2H), 7.62-7.65 (m, 1H),7.20 (t, 1H, J=7.5 Hz), 7.07-7.09 (m, 1H), 6.65 (s, 1H), 3.71 (s, 3H),2.98 (s, 4H), 2.49-2.64 (m, 2H), 1.35-1.41 (m, 2H), 0.98 (s, 9H).

Example 66 Synthesis of(E)-3-[2,6-difluoro-4-(5-pentyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1320)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.73 (d, 1H,J=7.6 Hz), 7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.80 (s,3H), 1.40-1.55 (m, 2H), 1.20-1.30 (m, 6H), 0.86 (t, 3H, J=7.0 Hz).

Example 67 Synthesis of(E)-3-[2,6-dichloro-4-(5-pentyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1321)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 8.28 (s, 2H), 7.73 (d, 1H, J=7.6 Hz),7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.69 (s, 3H),1.40-1.55 (m, 2H), 1.20-1.30 (m, 6H), 0.86 (t, 3H, J=7.0 Hz).

Example 68 Synthesis of(E)-3-[2,6-difluoro-4-(5-heptyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1322)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7-96 (s, 1H), 7.93 (s, 1H), 7.73 (d, 1H,J=7.6 Hz), 7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.80 (s,3H), 1.40-1.55 (m, 2H), 1.20-1.30 (m, 10H), 0.86 (t, 3H, J=7.0 Hz).

Example 69 Synthesis of(E)-3-[2,6-difluoro-4-(5-pent-1-ynyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1323)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.91-7.99 (m, 2H), 7.70-7.73 (m, 1H),7.33 (s, 1H), 7.24-7.30 (m, 2H), 3.18 (t, 2H, J=7.5 Hz), 3.01 (t, 2H,J=7.8 Hz), 2.42-2.54 (m, 2H), 1.80 (s, 3H), 1.55-1.66 (m, 2H), 1.04 (t,3H, J=7.5 Hz).

Example 70 Synthesis of(E)-3-[2,6-difluoro-4-(6-hept-1-ynyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1324)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.92-8.00 (m, 2H), 7.71 (t, 1H, J=3.9Hz), 7.34 (s, 1H), 7.28 (d, 2H, J=3.6 Hz), 3.17 (t, 2H, J=7.8 Hz), 3.01(t, 2H, J=8.1 Hz), 1.81 (s, 3H), 1.55-1.64 (m, 2H), 1.29-1.49 (m, 4H),0.91 (t, 3H, J=7.2 Hz).

Example 71 Synthesis of(E)-3-[4-(6-dec-1-ynyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (A1325)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 7.95 (d, 2H, J=7.8 Hz), 7.71 (t, 1H,J=4-8 Hz), 7.27-7.34 (m, 3H), 3.17 (t, 2H, J=8.1 Hz), 3.01 (t, 2H, J=8.1Hz), 1.81 (s, 3H), 1.20-1.60 (m, 12H), 0.84-0.88 (m, 3H).

Example 72 Synthesis of(E)-3-{2,6-difluoro-4-[6-(4-methylpent-1-ynyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A 1326)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.96 (d, 2H, J=8.4 Hz), 7.70-7.73 (m,1H), 7.23-7.34 (m, 3H), 3.18 (t, 2H, J=8.4 Hz), 3.02 (t, 2H, J=8.1 Hz),2.40 (d, 2H, J=6.3 Hz), 1.85-1.94 (m, 1H), 1.81 (s, 3H), 2.07 (d, 6H,J=6.6 Hz).

Example 73 Synthesis of(E)-3-[2,6-dichloro-4-(5-heptyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A 1327)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 8.26 (s, 2H), 7.73 (d, 1H, J=7.6 Hz),7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.69 (s, 3H),1.40-1.55 (m, 2H), 1.20-1.30 (m, 10H), 0.86 (t, 3H, J=7.0 Hz).

Example 74 Synthesis of(E)-3-[4-(5-butyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (A1328)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.73 (d, 1H,J=7.6 Hz), 7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.80 (s,3H), 1.40-1.55 (m, 2H), 1.20-1.30 (m, 4H), 0.86 (t, 3H, J=7.0 Hz).

Example 75 Synthesis of(E)-3-[4-(5-butyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)-2,6-dichlorophenyl]-2-methylacrylicacid (A1329)

1H-NMR(DMSO-d6) 12.91 (bs, 1H), 8.27 (s, 2H), 7.70 (d, 1H, J=7.6 Hz),7.39 (s, 1H), 7.22-7.35 (m, 3H), 2.94-3.16 (m, 3H), 1.69 (s, 3H),1.40-1.55 (m, 2H), 1.20-1.30 (m, 4H), 0.86 (t, 3H, J=7.0 Hz).

Example 76 Synthesis of(E)-3-[4-(6-cyclohexyl-1-enylethynyl-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (A1330)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.92-8.00 (m, 2H), 7.72-7.75 (m, 1H),7.29-7.38 (m, 3H), 6.20-6.28 (m, 1H), 3.17 (t, 2H, J=7.5 Hz), 3.02 (t,2H, J=7.5 Hz), 2.06-2.26 (m, 4H), 1.81 (s, 3H), 1.54-1.70 (m, 4H).

Example 77 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-methyloxyprop-1-ynyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1331)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.92-8.00 (m, 2H), 7.75-7.80 (m, 1H),7.29-7.38 (m, 3H), 4.40 (s, 2H), 3.37 (s, 3H), 3.20 (t, 2H, J=6.6 Hz),3.03 (t, 2H, J=6.6 Hz), 1.80 (s, 3H).

Example 78 Synthesis of(E)-3-{2,6-dichloro-4-[6-(3-ethyloxypentyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (A1332)

1H-NMR(CDCl3) 7.72 (s, 2H), 7.25 (s, 2H), 6.99 (d, 1H, J=7.6 Hz), 6.94(t, 1H, J=7.6 Hz), 4.27 (q, 2H, J=7.0 Hz), 3.49-3.56 (m, 2H), 3.20-3.25(m, 1H), 2.95-3.11 (m, 4H), 2.60-2.80 (m, 2H), 1.60-1.69 (m, 2H), 1.61(s, 3H), 1.45-1.55 (m, 2H), 1.48 (t, 3H, J=7.0 Hz), 1.28 (t, 3H, J=7.0Hz), 0.86 (t, 3H, J=7.2 Hz).

The compounds described below can be synthesized by similar methoddescribed above.

wherein R⁶, R⁷, and R⁸ are independently fluoro, chloro, or methyl;

R^(E) is n-pentyl, 3,3-dimethylbutyl, 1-methyoxyethyl,1-methyloxypropyl, 1-methyloxybutyl, 1-methyloxy-2-methylpropyl,1-methyloxypentyl, 1-methyloxy-3-methylbutyl,1-methyloxy-2,2-dimethylpropyl, 1-methyloxyhexyl,1-methyloxy-3,3-dimethylbutyl, 1-ethyloxyethyl, 1-ethyloxypropyl,1-ethyloxybutyl, 1-ethyloxy-2-methylpropyl, 1-ethyloxypentyl,1-ethyloxy-3-methylbutyl, 1-ethyloxy-2,2-dimethylpropyl,1-ethyloxyhexyl, 1-ethyloxy-3,3-dimethylbutyl, 1-n-propyloxymethyl,1-n-propyloxypropyl, 1-n-propyloxybutyl, 1-n-propyloxy-2-methylpropyl,1-n-propyloxypentyl, 1-n-propyloxy-3-methylbutyl,1-n-propyloxy-2,2-dimethylpropyl, 1-n-propyloxyhexyl,1-n-propyloxy-3,3-dimethylbutyl, 1-isopropyloxyethyl,1-isopropyloxypropyl, 1-isopropyloxybutyl,1-isopropyloxy-2-methylpropyl, 1-isopropyloxypentyl,1-isopropyloxy-3-methylbutyl, 1-isopropyloxy-2,2-dimethylpropyl,1-isopropyloxyhexyl, 1-isopropyloxy-3,3-dimethylbutyl,1-n-butyloxymethyl, 1-n-butyloxypropyl, 1-n-butyloxybutyl,1-n-butyloxy-2-methylpropyl, 1-n-butyloxypentyl,1-n-butyloxy-3-methylbutyl, 1-n-butyloxy-2,2-dimethylpropyl,1-isobutyloxyhexyl, 1-isobutyloxy-3,3-dimethylbutyl, 1-isobutyloxyethyl,1-isobutyloxypropyl, 1-isobutyloxybutyl, 1-isobutyloxy-2-methylpropyl,1-isobutyloxypentyl, 1-isobutyloxy-3-methylbutyl,1-isobutyloxy-2,2-dimethylpropyl, 1-isobutyloxyhexyl,1-isobutyloxy-3,3-dimethylbutyl, 1-t-butyloxyethyl, 1-t-butyloxypropyl,1-t-butyloxybutyl, 1-t-butyloxy-2-methylpropyl, 1-t-butyloxypentyl,1-t-butyloxy-3-methylbutyl, 1-t-butyloxy-2,2-dimethylpropyl,1-t-butyloxyhexyl, 1-t-butyloxy-3,3-dimethylbutyl, 1-n-pentyloxyethyl,1-n-pentyloxypropyl, 1-n-pentyloxybutyl, 1-n-pentyloxy-2-methylpropyl,1-n-pentyloxypentyl, 1-n-pentyloxy-3-methylbutyl,1-n-pentyloxy-2,2-dimethylpropyl, 1-n-pentyloxyhexyl,1-n-pentyloxy-3,3-dimethylbutyl, 1-neopentyloxyethyl,1-neopentyloxypropyl, 1-neopentyloxybutyl,1-neopentyloxy-2-methylpropyl, 1-neopentyloxypentyl,1-neopentyloxy-3-methylbutyl, 1-neopentyloxy-2,2-dimethylpropyl,1-neopentyloxyhexyl, 1-neopentyloxy-3,3-dimethylbutyl,3-methyloxypropyl, 3-methyloxybutyl, 3-methyloxypentyl,3-methyloxyhexyl, 3-methyloxy-4-methylpentyl, 3-methyloxyheptyl,3-methyloxy-5-methylhexyl, 3-methyloxy-4,4-dimethylpentyl,3-methyloxyoctyl, 3-methyloxy-5,5-dimethylhexyl, 3-ethyloxypropyl,3-ethyloxybutyl, 3-ethyloxypentyl, 3-ethyloxyhexyl,3-ethyloxy-4-methylpentyl, 3-ethyloxyheptyl, 3-ethyloxy-5-methylhexyl,3-ethyloxy-4,4-dimethylpentyl, 3-ethyloxyoctyl,3-ethyloxy-5,5-dimethylhexyl, 3-n-propyloxypropyl, 3-n-propyloxybutyl,3-n-propyloxypentyl, 3-n-propyloxyhexyl, 3-n-propyloxy-4-methylpentyl,3-n-propyloxyheptyl, 3-n-propyloxy-5-methylhexyl,3-n-propyloxy-4,4-dimethylpentyl, 3-n-propyloxyoctyl,3-n-propyloxy-5,5-dimethylhexyl, 3-isopropyloxypropyl,3-isopropyloxybutyl, 3-isopropyloxypentyl, 3-isopropyloxyhexyl,3-isopropyloxy-4-methylpentyl, 3-isopropyloxyheptyl,3-isopropyloxy-5-methylhexyl, 3-isopropyloxy-4,4-dimethylpentyl,3-isopropyloxyoctyl, 3-isopropyloxy-5,5-dimethylhexyl,3-n-butyloxypropyl, 3-n-butyloxybutyl, 3-n-butyloxypentyl,3-n-butyloxyhexyl, 3-n-butyloxy-4-methylpentyl, 3-n-butyloxyheptyl,3-n-butyloxy-5-methylhexyl, 3-n-butyloxy-4,4-dimethylpentyl,3-n-butyloxyoctyl, 3-n-butyloxy-5,5-dimethylhexyl, 3-isobutyloxypropyl,3-isobutyloxybutyl, 3-isobutyloxypentyl, 3-isobutyloxyhexyl,3-isobutyloxy-4-methylpentyl, 3-isobutyloxyheptyl,3-isobutyloxy-5-methylhexyl, 3-isobutyloxy-4,4-dimethylpentyl,3-isobutyloxyoctyl, 3-isobutyloxy-5,5-dimethylhexyl, 3-t-butyloxypropyl,3-t-butyloxybutyl, 3-t-butylcxypentyl, 3-t-butyloxyhexyl,3-t-butyloxy-4-methylpentyl, 3-t-butyloxyheptyl,3-t-butyloxy-5-methylhexyl, 3-t-butyloxy-4,4-dimethylpentyl,3-t-butyloxyoctyl, 3-t-butyloxy-5,5-dimethylhexyl, 3-n-pentyloxypropyl,3-n-pentyloxybutyl, 3-n-pentyloxypentyl, 3-n-pentylxyhexyl,3-n-pentyloxy-4-methylpentyl, 3-n-pentyloxyheptyl,3-n-pentyloxy-5-methylhexyl, 3-n-pentyloxy-4,4-dimethylpentyl,3-n-pentyloxyoctyl, or 3-n-pentyloxy-5,5-dimethylhexyl;

Z is ethylene or oxymethylene.

(Compound No., R⁶, R⁷, R⁸, R^(E), Z)=(A13, F, F, Me, 1-methyloxyethyl,CH2CH2), (A14, F, F, Me, 1-methyloxypropyl, CH2CH2), (A15, F, F, Me,1-methyloxybutyl, CH2CH2), (A16, F, F, Me, 1-methyloxy-2-methylpropyl,CH2CH2), (A17, F, F, Me, 1-methyloxypentyl, CH2CH2), (A18, F, F, Me,1-methyloxy-3-methylbutyl, CH2CH2), (A19, F, F, Me,1-methyloxy-2,2-dimethylpropyl, CH2CH2), (A20, F, F, Me,1-methyloxyhexyl, CH2CH2), (A21, F, F, Me,1-methyloxy-3,3-dimethylbutyl, CH2CH2), (A22, F, F, Me, 1-ethyloxyethyl,CH2CH2), (A23, F, F, Me, 1-ethyloxypropyl, CH2CH2), (A24, F, F, Me,1-ethyloxybutyl, CH2CH2), (A25, F, F, Me, 1-ethyloxy-2-methylpropyl,CH2CH2), (A26, F, F, Me, 1-ethyloxypentyl, CH2CH2), (A27, F, F, Me,1-ethyloxy-3-methylbutyl, CH2CH2), (A28, F, F, Me,1-ethyloxy-2,2-dimethylpropyl, CH2CH2), (A29, F, F, Me, 1-ethyloxyhexyl,CH2CH2), (A30, F, F, Me, 1-ethyloxy-3,3-dimethylbutyl, CH2CH2), (A31, F,F, Me, 1-n-propyloxymethyl, CH2CH2), (A32, F, F, Me,1-n-propyloxypropyl, CH2CH2), (A33, F, F, Me, 1-n-propyloxybutyl,CH2CH2), (A34, F, F, Me, 1-n-propyloxy-2-methylpropyl, CH2CH2), (A35, F,F, Me, 1-n-propyloxypentyl, CH2CH2), (A36, F, F, Me,1-n-propyloxy-3-methylbutyl, CH2CH2), (A37, F, F, Me,1-n-propyloxy-2,2-dimethylpropyl, CH2CH2), (A38, F, F, Me,1-n-propyloxyhexyl, CH2CH2), (A39, F, F, Me,1-n-propyloxy-3,3-dimethylbutyl, CH2CH2), (A40, F, F, Me,1-isopropyloxyethyl, CH2CH2), (A41, F, F, Me, 1-isopropyloxypropyl,CH2CH2), (A42, F, F, Me, 1-isopropyloxybutyl, CH2CH2), (A43, F, F, Me,1-isopropyloxy-2-methylpropyl, CH2CH2), (A44, F, F, Me,1-isopropyloxypentyl, CH2CH2), (A45, F, F, Me,1-isopropyloxy-3-methylbutyl, CH2CH2), (A46, F, F, Me,1-isopropyloxy-2,2-dimethylpropyl, CH2CH2), (A47, F, F, Me,1-isopropyloxyhexyl, CH2CH2), (A48, F, F, Me,1-isopropyloxy-3,3-dimethylbutyl, CH2CH2), (A49, F, F, Me,1-n-butyloxyethyl, CH2CH2), (A50, F, F, Me, 1-n-butyloxypropyl, CH2CH2),(A51, F, F, Me, 1-n-butyloxybutyl, CH2CH2), (A52, F, F, Me,1-n-butyloxy-2-methylpropyl, CH2CH2), (A53, F, F, Me,1-n-butyloxypentyl, CH2CH2), (A54, F, F, Me, 1-n-butyloxy-3-methylbutyl,CH2CH2), (A55, F, F, Me, 1-n-butyloxy-2,2-dimethylpropyl, CH2CH2), (A56,F, F, Me, 1-n-butyloxyhexyl, CH2CH2), (A57, F, F, Me,1-n-butyloxy-3,3-dimethylbutyl, CH2CH2), (A58, F, F, Me,1-isobutyloxyethyl, CH2CH2), (A59, F, F, Me, 1-isobutyloxypropyl,CH2CH2), (A60, F, F, Me, 1-isobutyloxybutyl, CH2CH2), (A61, F, F, Me,1-isobutyloxy-2-methylpropyl, CH2CH2), (A62, F, F, Me,1-isobutyloxypentyl, CH2CH2), (A63, F, F, Me,1-isobutyloxy-3-methylbutyl, CH2CH2), (A64, F, F, Me,1-isobutyloxy-2,2-dimethylpropyl, CH2CH2), (A65, F, F, Me,1-isobutyloxyhexyl, CH2CH2), (A66, F, F, Me,1-isobutyloxy-3,3-dimethylbutyl, CH2CH2), (A67, F, F, Me,1-t-butyloxyethyl, CH2CH2), (A68, F, F, Me, 1-t-butyloxypropyl, CH2CH2),(A69, F, F, Me, 1-t-butyloxybutyl, CH2CH2), (A70, F, F, Me,1-t-butyloxy-2-methylpropyl, CH2CH2), (A71, F, F, Me,1-t-butyloxypentyl, CH2CH2), (A72, F, F, Me, 1-t-butyloxy-3-methylbutyl,CH2CH2), (A73, F, F, Me, 1-t-butyloxy-2,2-dimethylpropyl, CH2CH2), (A74,F, F, Me, 1-t-butyloxyhexyl, CH2CH2), (A75, F, F, Me,1-t-butyloxy-3,3-dimethylbutyl, CH2CH2), (A76, F, F, Me,1-n-pentyloxyethyl, CH2CH2), (A77, F, F, Me, 1-n-pentyloxypropyl,CH2CH2), (A78, F, F, Me, 1-n-pentyloxybutyl, CH2CH2), (A79, F, F, Me,1-n-pentyloxy-2-methylpropyl, CH2CH2), (A80, F, F, Me,1-n-pentyloxypentyl, CH2CH2), (A81, F, F, Me,1-n-pentyloxy-3-methylbutyl, CH2CH2), (A82, F, F, Me,1-n-pentyloxy-2,2-dimethylpropyl, CH2CH2), (A83, F, F, Me,1-n-pentyloxyhexyl, CH2CH2), (A84, F, F, Me,1-n-pentyloxy-3,3-dimethylbutyl, CH2CH2), (A85, F, F, Me,1-neopentyloxyethyl, CH2CH2), (A86, F, F, Me, 1-neopentyloxypropyl,CH2CH2), (A87, F, F, Me, 1-neopentyloxybutyl, CH2CH2), (A88, F, F, Me,1-neopentyloxy-2-methylpropyl, CH2CH2), (A89, F, F, Me,1-neopentyloxypentyl, CH2CH2), (A90, F, F, Me,1-neopentyloxy-3-methylbutyl, CH2CH2), (A91, F, F, Me,1-neopentyloxy-2,2-dimethylpropyl, CH2CH2), (A92, F, F, Me,1-neopentyloxyhexyl, CH2CH2), (A93, F, F, Me,1-neopentyloxy-3,3-dimethylbutyl, CH2CH2), (A94, F, F, OMe,1-methyloxyethyl, CH2CH2), (A95, F, F, OMe, 1-methyloxypropyl, CH2CH2),(A96, F, F, OMe, 1-methyloxybutyl, CH2CH2), (A97, F, F, OMe,1-methyloxy-2-methylpropyl, CH2CH2), (A98, F, F, OMe, 1-methyloxypentyl,CH2CH2), (A99, F, F, OMe, 1-methyloxy-3-methylbutyl, CH2CH2), (A00, F,F, OMe, 1-methyloxy-2,2-dimethylpropyl, CH2CH2), (A101, F, F, OMe,1-methyloxyhexyl, CH2CH2), (A102, F, F, OMe,1-methyloxy-3,3-dimethylbutyl, CH2CH2), (A103, F, F, OMe,1-ethyloxyethyl, CH2CH2), (A104, F, F, OMe, 1-ethyloxypropyl, CH2CH2),(A16, F, F, OMe, 1-ethyloxybutyl, CH2CH2), (A106, F, F, OMe,1-ethyloxy-2-methylpropyl, CH2CH2), (A107, F, F, OMe, 1-ethyloxypentyl,CH2CH2), (A108, F, F, OMe, 1-ethyloxy-3-methylbutyl, CH2CH2), (A109, F,F, OMe, 1-ethyloxy-2,2-dimethylpropyl, CH2CH2), (A110, F, F, OMe,1-ethyloxyhexyl, CH2CH2), (A111, F, F, OMe,1-ethyloxy-3,3-dimethylbutyl, CH2CH2), (A112, F, F, OMe,1-n-propyloxyethyl, CH2CH2), (A113, F, F, OMe, 1-n-propyloxypropyl,CH2CH2), (A114, F, F, OMe, 1-n-propyloxybutyl, CH2CH2), (A115, F, F,OMe, 1-n-propyloxy-2-methylpropyl, CH2CH2), (A116, F, F, OMe,1-n-propyloxypentyl, CH2CH2), (A117, F, F, OMe,1-n-propyloxy-3-methylbutyl, CH2CH2), (A118, F, F, OMe,1-n-propyloxy-2,2-dimethylpropyl, CH2CH2), (A119, F, F, OMe,1-n-propyloxyhexyl, CH2CH2), (A120, F, F, OMe,1-n-propyloxy-3,3-dimethylbutyl, CH21CH2), (A121, F, F, OMe,1-isopropyloxyethyl, CH2CH2), (A122, F, F, OMe, 1-isopropyloxypropyl,CH2CH2), (A123, F, F, OMe, 1-isopropyloxybutyl, CH2CH2), (A124, F, F,OMe, 1-isopropyloxy-2-methylpropyl, CH2CH2), (A125, F, F, OMe,1-isopropyloxypentyl, CH2CH2), (A126, F, F, OMe,1-isopropyloxy-3-methylbutyl, CH2CH2), (A127, F, F, OMe,1-isopropyloxy-2,2-dimethylpropyl, CH2CH2), (A128, F, F, OMe,1-isopropyloxyhexyl, CH2CH2), (A129, F, F, OMe,1-isopropyloxy-3,3-dimethylbutyl, CH2CH2), (A130, F, F, OMe,1-n-butyloxyethyl, CH2CH2), (A131, F, F, OMe, 1-n-butyloxypropyl,CH2CH2), (A132, F, F, OMe, 1-n-butyloxybutyl, CH2CH2), (A133, F, F, OMe,1-n-butyloxy-2-methylpropyl, CH2CH2), (A134, F, F, OMe,1-n-butyloxypentyl, CH2CH2), (A135, F, F, OMe,1-n-butyloxy-3-methylbutyl, CH2CH2), (A136, F, F, OMe,1-n-butyloxy-2,2-dimethylpropyl, CH2CH2), (A137, F, F, OMe,1-n-butyloxyhexyl, CH2CH2), (A138, F, F, OMe,1-n-butyloxy-3,3-dimethylbutyl, CH2CH2), (A139, F, F, OMe,1-isobutyloxyethyl, CH2CH2), (A140, F, F, OMe, 1-isobutyloxypropyl,CH2CH2), (A141, F, F, OMe, 1-isobutyloxybutyl, CH2CH2), (A142, F, F,OMe, 1-isobutyloxy-2-methylpropyl, CH2CH2), (A143, F, F, OMe,1-isobutyloxypentyl, CH2CH2), (A144, F, F, OMe,1-isobutyloxy-3-methylbutyl, CH2CH2), (A145, F, F, OMe,1-isobutyloxy-2,2-dimethylpropyl, CH2CH2), (A146, F, F, OMe,1-isobutyloxyhexyl, CH2CH2), (A147, F, F, OMe,1-isobutyloxy-3,3-dimethylbutyl, CH2CH2), (A148, F, F, OMe,1-t-butyloxyethyl, CH2CH2), (A149, F, F, OMe, 1-t-butyloxypropyl,CH2CH2), (A150, F, F, OMe, 1-t-butyloxybutyl, —CH2CH2), (A151, F, F,OMe, 1-t-butyloxy-2-methylpropyl, CH2CH2), (A152, F, F, OMe,1-t-butyloxypentyl, CH2CH2), (A153, F, F, OMe,1-t-butyloxy-3-methylbutyl, CH2CH2), (A154, F, F, OMe,1-t-butyloxy-2,2-dimethylpropyl, CH2CH2), (A155, F, F, OMe,1-t-butyloxyhexyl, CH2CH2), (A156, F, F, OMe,1-t-butyloxy-3,3-dimethylbutyl, CH2CH2), (A157, F, F, OMe,1-n-pentyloxyethyl, CH2CH2), (A158, F, F, OMe, 1-n-pentyloxypropyl,CH12CH2), (A159, F, F, OMe, 1-n-pentyloxybutyl, CH2CH2), (A160, F, F,OMe, 1-n-pentyloxy-2-methylpropyl, CH2CH2), (A161, F, F, OMe,1-n-pentyloxypentyl, CH2CH2), (A162, F, F, OMe,1-n-pentyloxy-3-methylbutyl, CH2CH2), (A163, F, F, OMe,1-n-pentyloxy-2,2-dimethylpropyl, CH2CH2), (A164, F, F, OMe,1-n-pentyloxyhexyl, CH2CH2), (A165, F, F, OMe,1-n-pentyloxy-3,3-dimethylbutyl, CH2CH2), (A166, F, F, OMe,1-neopentyloxyethyl, CH2CH2), (A167, F, F, OMe, 1-neopentyloxypropyl,CH2CH2), (A168, F, F, OMe, 1-neopentyloxybutyl, CH2CH2), (A169, F, F,OMe, 1-neopentyloxy-2-methylpropyl, CH2CH2), (A170, F, F, OMe,1-neopentyloxypentyl, CH2CH2), (A171, F, F, OMe,1-neopentyloxy-3-methylbutyl, CH2CH2), (A172, F, F, OMe,1-neopentyloxy-2,2-dimethylpropyl, CH2CH2), (A173, F, F, OMe,1-neopentyloxyhexyl, CH2CH2), (A174, F, F, OMe,1-neopentyloxy-3,3-dimethylbutyl, CH2CH2), (A175, F, F, Me,1-methyloxyethyl, OCH2), (A176, F, F, Me, 1-methyloxypropyl, OCH2),(A177, F, F, Me, 1-methyloxybutyl, OCH2), (A178, F, F, Me,1-methyloxy-2-methylpropyl, OCH2), (A179, F, F, Me, 1-methyloxypentyl,OCH2), (A180, F, F, Me, 1-methyloxy-3-methylbutyl, OCH2), (A181, F, F,Me, 1-methyloxy-2,2-dimethylpropyl, OCH2), (A182, F, F, Me,1-methyloxyhexyl, OCH2), (A183, F, F, Me, 1-methyloxy-3,3-dimethylbutyl,OCH2), (A184, F, F, Me, 1-ethyloxyethyl, OCH2), (A185, F, F, Me,1-ethyloxypropyl, OCH2), (A186, F, F, Me, 1-ethyloxybutyl, OCH2), (A187,F, F, Me, 1-ethyloxy-2-methylpropyl, OCH2), (A188, F, F, Me,1-ethyloxypentyl, OCH2), (A189, F, F, Me, 1-ethyloxy-3-methylbutyl,OCH2), (A190, F, F, Me, 1-ethyloxy-2,2-dimethylpropyl, OCH2), (A191, F,F, Me, 1-ethyloxyhexyl, OCH2), (A192, F, F, Me,1-ethyloxy-3,3-dimethylbutyl, OCH2), (A193, F, F, Me,1-n-propyloxyethyl, OCH2), (A194, F, F, Me, 1-n-propyloxypropyl, OCH2),(A195, F, F, Me, 1-n-propyloxybutyl, OCH2), (A196, F, F, Me,1-n-propyloxy-2-methylpropyl, OCH2), (A197, F, F, Me,1-n-propyloxypentyl, OCH2), (A198, F, F, Me,1-n-propyloxy-3-methylbutyl, OCH2), (A199, F, F, Me,1-n-propyloxy-2,2-dimethylpropyl, OCH2), (A200, F, F, Me,1-n-propyloxyhexyl, OCH2), (A201, F, F, Me,1-n-propyloxy-3,3-dimethylbutyl, OCH2), (A202, F, F, Me,1-isopropyloxyethyl, OCH2), (A₂O₃, F, F, Me, 1-isopropyloxypropyl,OCH2), (A204, F, F, Me, 1-isopropyloxybutyl, OCH2), (A205, F, F, Me,1-isopropyloxy-2-methylpropyl, OCH2), (A206, F, F, Me,1-isopropyloxypentyl, OCH2), (A207, F, F, Me,1-isopropyloxy-3-methylbutyl, OCH2), (A208, F, F, Me,1-isopropyloxy-2,2-dimethylpropyl, OCH2), (A209, F, F, Me,1-isopropyloxyhexyl, OCH2), (A210, F, F, Me,1-isopropyloxy-3,3-dimethylbutyl, OCH2), (A211, F, F, Me,1-n-butyloxyethyl, OCH2), (A212, F, F, Me, 1-n-butyloxypropyl, OCH2),(A213, F, F, Me, 1-n-butyloxybutyl, OCH2), (A214, F, F, Me,1-n-butyloxy-2-methylpropyl, OCH2), (A215, F, F, Me, 1-n-butyloxypentyl,OCH2), (A216, F, F, Me, 1-n-butyloxy-3-methylbutyl, OCH2), (A217, F, F,Me, 1-n-butyloxy-2,2-dimethylpropyl, OCH2), (A218, F, F, Me,1-n-butyloxyhexyl, OCH2), (A219, F, F, Me,1-n-butyloxy-3,3-dimethylbutyl, OCH2), (A220, F, F, Me,1-isobutyloxyethyl, OCH2), (A221, F, F, Me, 1-isobutyloxypropyl, OCH2),(A222, F, F, Me, 1-isobutyloxybutyl, OCH2), (A223, F, F, Me,1-isobutyloxy-2-methylpropyl, OCH2), (A224, F, F, Me,1-isobutyloxypentyl, OCH2), (A225, F, F, Me,1-isobutyloxy-3-methylbutyl, OCH2), (A226, F, F, Me,1-isobutyloxy-2,2-dimethylpropyl, OCH2), (A227, F, F, Me,1-isobutyloxyhexyl, OCH2), (A228, F, F, Me,1-isobutyloxy-3,3-dimethylbutyl, OCH2), (A229, F, F, Me,1-t-butyloxyethyl, OCH2), (A230, F, F, Me, 1-t-butyloxypropyl, OCH2),(A231, F, F, Me, 1-t-butyloxybutyl, OCH2), (A232, F, F, Me,1-t-butyloxy-2-methylpropyl, OCH2), (A233, F, F, Me, 1-t-butyloxypentyl,OCH2), (A234, F, F, Me, 1-t-butyloxy-3-methylbutyl, OCH2), (A235, F, F,Me, 1-t-butyloxy-2,2-dimethylpropyl, OCH2), (A236, F, F, Me,1-t-butyloxyhexyl, OCH2), (A237, F, F, Me,1-t-butyloxy-3,3-dimethylbutyl, OCH2), (A238, F, F, Me,1-n-pentyloxyethyl, OCH2), (A239, F, F, Me, 1-n-pentlyloxypropyl, OCH2),(A240, F, F, Me, 1-n-pentyloxybutyl, OCH2), (A241, F, F, Me,1-n-pentyloxy-2-methylpropyl, OCH2), (A242, F, F, Me,1-n-pentyloxypentyl, OCH2), (A243, F, F, Me,1-n-pentyloxy-3-methylbutyl, OCH2), (A244, F, F, Me,1-n-pentyloxy-2,2-dimethylpropyl, OCH2), (A245, F, F, Me,1-n-pentyloxyhexyl, OCH2), (A246, F, F, Me,1-n-pentyloxy-3,3-dimethylbutyl, OCH2), (A247, F, F, Me,1-neopentyloxyethyl, OCH2), (A248, F, F, Me, 1-neopentyloxypropyl,OCH2), (A249, F, F, Me, 1-neopentyloxybutyl, OCH2), (A250, F, F, Me,1-neopentyloxy-2-methylpropyl, OCH2), (A251, F, F, Me,1-neopentyloxypentyl, OCH2), (A252, F, F, Me,1-neopentyloxy-3-methylbutyl, OCH2), (A253, F, F, Me,1-neopentyloxy-2,2-dimethylpropyl, OCH2), (A254, F, F, Me,1-neopentyloxyhexyl, OCH2), (A255, F, F, Me,1-neopentyloxy-3,3-dimethylbutyl, OCH2), (A256, F, F, OMe,1-methyloxyethyl, OCH2), (A257, F, F, OMe, 1-methyloxypropyl, OCH2),(A258, F, F, OMe, 1-methyloxybutyl, OCH2), (A259, F, F, OMe,1-methyloxy-2-methylpropyl, OCH2), (A260, F, F, OMe, 1-methyloxypentyl,OCH2), (A261, F, F, OMe, 1-methyloxy-3-methylbutyl, OCH2), (A262, F, F,OMe, 1-methyloxy-2,2-dimethylpropyl, OCH2), (A263, F, F, OMe,1-methyloxyhexyl, OCH2), (A264, F, F, OMe,1-methyloxy-3,3-dimethylbutyl, OCH2), (A265, F, F, OMe, 1-ethyloxyethyl,OCH2), (A266, F, F, OMe, 1-ethyloxypropyl, OCH2), (A267, F, F, OMe,1-ethyloxybutyl, OCH2), (A268, F, F, OMe, 1-ethyloxy-2-methylpropyl,OCH2), (A269, F, F, OMe, 1-ethyloxypentyl, OCH2), (A270, F, F, OMe,1-ethyloxy-3-methylbutyl, OCH2), (A271, F, F, OMe,1-ethyloxy-2,2-dimethylpropyl, OCH2), (A272, F, F, OMe, 1-ethyloxyhexyl,OCH2), (A273, F, F, OMe, 1-ethyloxy-3,3-dimethylbutyl, OCH2), (A274, F,F, OMe, 1-n-propyloxyethyl, OCH2), (A275, F, F, OMe,1-n-propyloxypropyl, OCH2), (A276, F, F, OMe, 1-n-propyloxybutyl, OCH2),(A277, F, F, OMe, 1-n-propyloxy-2-methylpropyl, OCH2), (A278, F, F, OMe,1-n-propyloxypentyl, OCH2), (A279, F, F, OMe,1-n-propyloxy-3-methylbutyl, OCH2), (A280, F, F, OMe,1-n-propyloxy-2,2-dimethylpropyl, OCH2), (A281, F, F, OMe,1-n-propyloxyhexyl, OCH2), (A282, F, F, OMe,1-n-propyloxy-3,3-dimethylbutyl, OCH2), (A283, F, F, OMe,1-isopropyloxyethyl, OCH2), (A284, F, F, OMe, 1-isopropyloxypropyl,OCH2), (A285, F, F, OMe, 1-isopropyloxybutyl, OCH2), (A286, F, F, OMe,1-isopropyloxy-2-methylpropyl, OCH2), (A287, F, F, OMe,1-isopropyloxypentyl, OCH2), (A288, F, F, OMe,1-isopropyloxy-3-methylbutyl, OCH2), (A289, F, F, OMe,1-isopropyloxy-2,2-dimethylpropyl, OCH2), (A290, F, F, OMe,1-isopropyloxyhexyl, OCH2), (A291, F, F, OMe,1-isopropyloxy-3,3-dimethylbutyl, OCH2), (A292, F, F, OMe,1-n-butyloxyethyl, OCH2), (A293, F, F, OMe, 1-n-butyloxypropyl, OCH2),(A294, F, F, OMe, 1-n-butyloxybutyl, OCH2), (A295, F, F, OMe,1-n-butyloxy-2-methylpropyl, OCH2), (A296, F, F, OMe,1-n-butyloxypentyl, —OCH2), (A297, F, F, OMe,1-n-butyloxy-3-methylbutyl, OCH2), (A298, F, F, OMe,1-n-butyloxy-2,2-dimethylpropyl, OCH2), (A299, F, F, OMe,1-n-butyloxyhexyl, OCH2), (A300, F, F, OMe,1-n-butyloxy-3,3-dimethylbutyl, OCH2), (A301, F, F, OMe,1-isobutyloxyethyl, OCH2), (A302, F, F, OMe, 1-isobutyloxypropyl, OCH2),(A303, F, F, OMe, 1-isobutyloxybutyl, OCH2), (A304, F, F, OMe,1-isobutyloxy-2-methylpropyl, OCH2), (A305, F, F, OMe,1-isobutyloxypentyl, OCH2), (A306, F, F, OMe,1-isobutyloxy-3-methylbutyl, OCH2), (A307, F, F, OMe,1-isobutyloxy-2,2-dimethylpropyl, OCH2), (A308, F, F, OMe,1-isobutyloxyhexyl, OCH2), (A309, F, F, OMe,1-isobutyloxy-3,3-dimethylbutyl, OCH2), (A310, F, F, OMe,1-t-butyloxyethyl, OCH2), (A311, F, F, OMe, 1-t-butyloxypropyl, OCH2),(A312, F, F, OMe, 1-t-butyloxybutyl, OCH2), (A313, F, F, OMe,1-t-butyloxy-2-methylpropyl, OCH2), (A314, F, F, OMe,1-t-butyloxypentyl, OCH2), (A315, F, F, OMe, 1-t-butyloxy-3-methylbutyl,OCH2), (A316, F, F, OMe, 1-t-butyloxy-2,2-dimethylpropyl, OCH2), (A317,F, F, OMe, 1-t-butyloxyhexyl, OCH2), (A318, F, F, OMe,1-t-butyloxy-3,3-dimethylbutyl, OCH2), (A319, F, F, OMe,1-n-pentyloxyethyl, OCH2), (A320, F, F, OMe, 1-n-pentyloxypropyl, OCH2),(A321, F, F, OMe, 1-n-pentyloxybutyl, OCH2), (A322, F, F, OMe,1-n-pentyloxy-2-methylpropyl, OCH2), (A323, F, F, OMe,1-n-pentyloxypentyl, OCH2), (A324, F, F, OMe,1-n-pentyloxy-3-methylbutyl, OCH2), (A325, F, F, OMe,1-n-pentyloxy-2,2-dimethylpropyl, OCH2), (A326, F, F, OMe,1-n-pentyloxyhexyl, OCH2), (A327, F, F, OMe,1-n-pentyloxy-3,3-dimethylbutyl, OCH2), (A328, F, F, OMe,1-neopentyloxyethyl, OCH2), (A329, F, F, OMe, 1-neopentyloxypropyl,OCH2), (A330, F, F, OMe, 1-neopentyloxybutyl, OCH2), (A331, F, F, OMe,1-neopentyloxy-2-methylpropyl, OCH2), (A332, F, F, OMe,1-neopentyloxypentyl, OCH2), (A333, F, F, OMe,1-neopentyloxy-3-methylbutyl, OCH2), (A334, F, F, OMe,1-neopentyloxy-2,2-dimethylpropyl, OCH2), (A335, F, F, OMe,1-neopentyloxyhexyl, OCH2), (A336, F, F, OMe,1-neopentyloxy-3,3-dimethylbutyl, OCH2), (A337, F, F, Me,3-methyloxypropyl, CH2CH2), (A338, F, F, Me, 3-methyloxybutyl, CH2CH2),(A340, F, F, Me, 3-methyloxy-4-methylpentyl, CH2CH2), (A342, F, F, Me,3-methyloxy-5-methylhexyl, CH2CH2), (A343, F, F, Me, 3-methyloxyoctyl,CH2CH2), (A344, F, F, Me, 3-methyloxy-5,5-dimethylhexyl, CH2CH2), (A345,F, F, Me, 3-ethyloxybutyl, CH2CH2), (A348, F, F, Me,3-ethyloxy-4-methylpentyl, CH2CH2), (A350, F, F, Me,3-ethyloxy-5-methylhexyl, CH2CH2), (A352, F, F, Me, 3-ethyloxyoctyl,CH2CH2), (A353, F, F, Me, 3-ethyloxy-5,5-dimethylhexyl, CH2CH2), (A354,F, F, Me, 3-n-propyloxybutyl, CH2CH2), (A355, F, F, Me,3-n-propyloxypentyl, CH2CH2), (A356, F, F, Me, 3-n-propyloxyhexyl,CH2CH2), (A357, F, F, Me, 3-n-propyloxy-4-methylpentyl, CH2CH2), (A358,F, F, Me, 3-n-propyloxyheptyl, CH2CH2), (A359, F, F, Me,3-n-propyloxy-5-methylhexyl, CH2CH2), (A360, F, F, Me,3-n-propyloxy-4,4-dimethylpentyl, CH2CH2), (A361, F, F, Me,3-n-propyloxyoctyl, CH2CH2), (A362, F, F, Me,3-n-propyloxy-5,5-dimethylhexyl, CH2CH2), (A363, F, F, Me,3-isopropyloxybutyl, CH2CH2), (A364, F, F, Me, 3-isopropyloxypentyl,CH2CH2), (A365, F, F, Me, 3-isopropyloxyhexyl, CH2CH2), (A366, F, F, Me,3-isopropyloxy-4-methylpentyl, CH2CH2), (A367, F, F, Me,3-isopropyloxyheptyl, CH2CH2), (A368, F, F, Me,3-isopropyloxy-5-methylhexyl, CH2CH2), (A369, F, F, Me,3-isopropyloxy-4,4-dimethylpentyl, CH2CH2), (1A370, F, F, Me,3-isopropyloxyoctyl, CH2CH2), (A371, F, F, Me,3-isopropyloxy-5,5-dimethylhexyl, CH2CH2), (A372, F, F, Me,3-n-butyloxybutyl, CH2CH2), (A373, F, F, Me, 3-n-butyloxypentyl,CH2CH2), (A374, F, F, Me, 3-n-butyloxyhexyl, CH2CH2), (A375, F, F, Me,3-n-butyloxy-4-methylpentyl, CH2CH2), (A376, F, F, Me,3-n-butyloxyheptyl, CH2CH2), (A377, F, F, Me,3-n-butyloxy-5-methylhexyl, CH2CH2), (A378, F, F, Me,3-n-butyloxy-4,4-dimethylpentyl, CH2CH2), (A379, F, F, Me,3-n-butyloxyoctyl, CH2CH2), (A380, F, F, Me,3-n-butyloxy-5,5-dimethylhexyl, CH2CH2), (A381, F, F, Me,3-isobutyloxypropyl, CH2CH2), (A382, F, F, Me, 3-isobutyloxybutyl,CH2CH2), (A383, F, F, Me, 3-isobutyloxypentyl, CH2CH2), (A384, F, F, Me,3-isobutyloxyhexyl, CH2CH2), (A385, F, F, Me,3-isobutyloxy-4-methylpentyl, CH2CH2), (A386, F, F, Me,3-isobutyloxyheptyl, CH2CH2), (A387, F, F, Me,3-isobutyloxy-5-methylhexyl, CH2CH2), (A388, F, F, Me,3-isobutyloxy-4,4-dimethylpentyl, CH2CH2), (A389, F, F, Me,3-isobutyloxyoctyl, CH2CH2), (A390, F, F, Me,3-isobutyloxy-5,5-dimethylhexyl, CH2CH2), (A391, F, F, Me,3-t-butyloxypropyl, CH2CH2), (A392, F, F, Me, 3-t-butyloxybutyl,CH2CH2), (A393, F, F, Me, 3-t-butyloxypentyl, CH2CH2), (A394, F, F, Me,3-t-butyloxyhexyl, CH2CH2), (A395, F, F, Me,3-t-butyloxy-4-methylpentyl, CH2CH2), (A396, F, F, Me,3-t-butyloxyheptyl, CH2CH2), (A397, F, F, Me,3-t-butyloxy-5-methylhexyl, CH2CH2), (A398, F, F, Me,3-t-butyloxy-4,4-dimethylpentyl, CH2CH2), (A399, F, F, Me,3-t-butyloxyoctyl, CH2CH2), (A400, F, F, Me,3-t-butyloxy-5,5-dimethylhexyl, CH2CH2), (A402, F, F, Me,3-n-pentyloxybutyl, CH2CH2), (A403, F, F, Me, 3-n-pentyloxypentyl,CH2CH2), (A404, F, F, Me, 3-n-pentyloxyhexyl, CH2CH2), (A405, F, F, Me,3-n-pentyloxy-4-methylpentyl, CH2CH2), (A406, F, F, Me,3-n-pentyloxyheptyl, CH2CH2), (A407, F, F, Me,3-n-pentyloxy-5-methylhexyl, CH2CH2), (A408, F, F, Me,3-n-pentyloxy-4,4-dimethylpentyl, CH2CH2), (A409, F, F, Me,3-n-pentyloxyoctyl, CH2CH2), (A410, F, F, Me,3-n-pentyloxy-5,5-dimethylhexyl, CH2CH2), (A411, F, F, Me,3-neopentyloxybutyl, CH2CH2), (A412, F, F, Me, 3-neopentyloxypentyl,CH2CH2), (A413, F, F, Me, 3-neopentyloxyhexyl, CH2CH2), (A414, F, F, Me,3-neopentyloxy-4-methylpentyl, CH2CH2), (A415, F, F, Me,3-neopentyloxyheptyl, CH2CH2), (A416, F, F, Me,3-neopentyloxy-5-methylhexyl, CH2CH2), (A417, F, F, Me,3-neopentyloxy-4,4-dimethylpentyl, CH2CH2), (A418, F, F, Me,3-neopentyloxyoctyl, CH2CH2), (A419, F, F, Me,3-neopentyloxy-5,5-dimethylhexyl, CH2CH2), (A420, F, F, OMe,3-methyloxypropyl, CH2CH2), (A421, F, F, OMe, 3-methyloxybutyl, CH2CH2),(A422, F, F, OMe, 3-methyloxypentyl, CH2CH2), (A424, F, F, OMe,3-methyloxy-4-methylpentyl, CH2CH2), (A425, F, F, OMe,3-methyloxyheptyl, CH2CH2), (A426, F, F, OMe, 3-methyloxy-5-methylhexyl,CH2CH2), (A427, F, F, OMe, 3-methoxy-4,4-dimethylpentyl, CH2CH2), (A428,F, F, OMe, 3-methyloxyoctyl, CH2CH2), (A429, F, F, OMe,3-methyloxy-5,5-dimethylhexyl, CH2CH2), (A431, F, F, OMe,3-ethyloxybutyl, CH2CH2), (A432, F, F, OMe, 3-ethyloxypentyl, CH2CH2),(A433, F, F, OMe, 3-ethyloxyhexyl, CH2CH2), (A434, F, F, OMe,3-ethyloxy-4-methylpentyl, CH2CH2), (A435, F, F, OMe, 3-ethyloxyheptyl,CH2CH2), (A436, F, F, OMe, 3-ethyloxy-5-methylhexyl, CH2CH2), (A437, F,F, OMe, 3-ethyloxy-4,4-dimethylpentyl, CH2CH2), (A438, F, F, OMe,3-ethyloxyoctyl, CH2CH2), (A439, F, F, OMe,3-ethyloxy-5,5-dimethylhexyl, CH2CH2), (A441, F, F, OMe,3-n-propyloxybutyl, CH2CH2), (A442, F, F, OMe, 3-n-propyloxypentyl,CH2CH2), (A443, F, F, OMe, 3-n-propyloxyhexyl, CH2CH2), (A444, F, F,OMe, 3-n-propyloxy-4-methylpentyl, CH2CH2), (A445, F, F, OMe,3-n-propyloxyheptyl, CH2CH2), (A446, F, F, OMe,3-n-propyloxy-5-methylhexyl, CH2CH2), (A447, F, F, OMe,3-n-propyloxy-4,4-dimethylpentyl, CH2CH2), (A448, F, F, OMe,3-n-propyloxyoctyl, CH2CH2), (A449, F, F, OMe,3-n-propyloxy-5,5-dimethylhexyl, CH2 CH2), (A451, F, F, OMe,3-isopropyloxybutyl, CH2CH2), (A452, F, F, OMe, 3-isopropyloxypentyl,CH2CH2), (A453, F, F, OMe, 3-isopropyloxyhexyl, CH2CH2), (A454, F, F,OMe, 3-isopropyloxy-4-methylpentyl, CH2CH2), (A455, F, F, OMe,3-isopropyloxyheptyl, CH2CH2), (A456, F, F, OMe,3-isopropyloxy-5-methylhexyl, CH2CH2), (A457, F, F, OMe,3-isopropyloxy-4,4-dimethylpentyl, CH2CH2), (A458, F, F, OMe,3-isopropyloxyoctyl, CH2CH2), (A459, F, F, OMe,3-isopropyloxy-5,5-dimethylhexyl, CH2CH2), (A460, F, F, OMe,3-n-butyloxypropyl, CH2CH2), (A461, F, F, OMe, 3-n-butyloxybutyl,CH2CH2), (A462, F, F, OMe, 3-n-butyloxypentyl, CH2CH2), (A463, F, F,OMe, 3-n-butyloxyhexyl, CH2CH2), (A464, F, F, OMe,3-n-butyloxy-4-methylpentyl, CH2CH2), (A465, F, F, OMe,3-n-butyloxyheptyl, CH2CH2), (A466, F, F, OMe,3-n-butyloxy-5-methylhexyl, CH2CH2), (A467, F, F, OMe,3-n-butyloxy-4,4-dimethylpentyl, CH2CH2), (A468, F, F, OMe,3-n-butyloxyoctyl, CH2CH2), (A469, F, F, OMe,3-n-butyloxy-5,5-dimethylhexyl, CH2CH2), (A470, F, F, OMe,3-isobutyloxypropyl, CH2CH2), (A471, F, F, OMe, 3-isobutyloxybutyl,CH2CH2), (A472, F, F, OMe, 3-isobutyloxypentyl, CH2CH2), (A473, F, F,OMe, 3-isobutyloxyhexyl, CH2CH2), (A474, F, F, OMe,3-isobutyloxy-4-methylpentyl, CH2CH2), (A475, F, F, OMe,3-isobutyloxyheptyl, CH2CH2), (A476, F, F, OMe,3-isobutyloxy-5-methylhexyl, CH2CH2), (A477, F, F, OMe,3-isobutyloxy-4,4-dimethylpentyl, CH2CH2), (A478, F, F, OMe,3-isobutyloxyoctyl, CH2CH2), (A479, F, F, OMe,3-isobutyloxy-5,5-dimethylhexyl, CH2CH2), (A480, F, F, OMe,3-t-butyloxypropyl, CH2CH2), (A481, F, F, OMe, 3-t-butyloxybutyl,CH2CH2), (A482, F, F, OMe, 3-t-butyloxypentyl, CH2CH2), (A483, F, F,OMe, 3-t-butyloxyhexyl, CH2CH2), (A484, F, F, OMe,3-t-butyloxy-4-methylpentyl, CH2CH2), (A485, F, F, OMe,3-t-butyloxyheptyl, CH2CH2), (A486, F, F, OMe,3-t-butyloxy-5-methylhexyl, CH2CH2), (A487, F, F, OMe,3-t-butyloxy-4,4-dimethylpentyl, CH2CH2), (A488, F, F, OM-e,3-t-butyloxyoctyl, CH2CH2), (A489, F, F, OMe,3-t-butyloxy-5,5-dimethylhexyl, CH2CH2), (A490, F, F, OMe,3-n-pentyloxypropyl, CH2CH2), (A491, F, F, OMe, 3-n-pentyloxybutyl,CH2CH2), (A492, F, F, OMe, 3-n-pentyloxypentyl, CH2CH2), (A493, F, F,OMe, 3-n-pentyloxyhexyl, CH2CH2), (A494, F, F, OMe,3-n-pentyloxy-4-methylpentyl, CH2CH2), (A495, F, F, OMe,3-n-pentyloxyheptyl, CH2CH2), (A496, F, F, OMe,3-n-pentyloxy-5-methylhexyl, CH2CH2), (A497, F, F, OMe,3-n-pentyloxy-4,4-dimethylpentyl, CH2CH2), (A498, F, F, OMe,3-n-pentyloxyoctyl, CH2CH2), (A499, F, F, OMe,3-n-pentyloxy-5,5-dimethylhexyl, CH2CH2), (A501, F, F, OMe,3-neopentyloxybutyl, (CH2CH2), (A502, F, F, OMe, 3-neopentyloxypentyl,CH2CH2), (A503, F, F, OMe, 3-neopentyloxyhexyl, CH2CH2), (A504, F, F,OMe, 3-neopentyloxy-4-methylpentyl, CH2CH2), (A505, F, F, OMe,3-neopentyloxyheptyl, CH2CH2), (A506, F, F, OMe,3-neopentyloxy-5-methylhexyl, CH2CH2), (A507, F, F, OMe,3-neopentyloxy-4,4-dimethylpentyl, CH2CH2), (A508, F, F, OMe,3-neopentyloxyoctyl, CH2CH2), (A509, F, F, OMe,3-neopentyloxy-5,5-dimethylhexyl, CH2CH2), (A510, F, F, OMe,3-methyloxypropyl, OCH2), (A611, F, F, OMe, 3-methyloxybutyl, OCH2),(A512, F, F, OMe, 3-methyloxypentyl, OCH2), (A513, F, F, OMe,3-methyloxyhexyl, OCH2), (A514, F, F, OMe, 3-methyloxy-4-methylpentyl,OCH2), (A515, F, F, OMe, 3-methyloxyheptyl, OCH2), (A516, F, F, OMe,3-methyloxy-5-methylhexyl, OCH2), (A517, F, F, OMe,3-methoxy-4,4-dimethylpentyl, OCH2), (A518, F, F, OMe, 3-methyloxyoctyl,OCH2), (A519, F, F, OMe, 3-methyloxy-5,5-dimethylhexyl, OCH2), (A520, F,F, OMe, 3-ethyloxypropyl, OCH2), (A521, F, F, OMe, 3-ethyloxybutyl,OCH2), (A522, F, F, OMe, 3-ethyloxypentyl, OCH2), (A523, F, F, OMe,3-ethyloxyhexyl, OCH2), (A524, F, F, OMe, 3-ethyloxy-4-methylpentyl,OCH2), (A525, F, F, OMe, 3-ethyloxyheptyl, OCH2), (A526, F, F, OMe,3-ethyloxy-5-methylhexyl, OCH2), (A527, F, F, OMe,3-ethyloxy-4,4-dimethylpentyl, OCH2), (A528, F, F, OMe, 3-ethyloxyoctyl,OCH2), (A529, F, F, OMe, 3-ethyloxy-5,5-dimethylhexyl, OCH2), (A530, F,F, OMe, 3-n-propyloxypropyl, OCH2), (A531, F, F, OMe,3-n-propyloxybutyl, OCH2), (A632, F, F, OMe, 3-n-propyloxypentyl, OCH2),(A533, F, F, OMe, 3-n-propyloxyhexyl, OCH2), (A534, F, F, OMe,3-n-propyloxy-4-methylpentyl, OCH2), (A535, F, F, OMe,3-n-propyloxyheptyl, OCH2), (A536, F, F, OMe,3-n-propyloxy-5-methylhexyl, OCH2), (A537, F, F, OMe,3-n-propyloxy-4,4-dimethylpentyl, OCH2), (A538, F, F, OMe,3-n-propyloxyoctyl, OCH2), (A539, F, F, OMe,3-n-propyloxy-5,6-dimethylhexyl, OCH2), (A540, F, F, OMe,3-isopropyloxypropyl, OCH2), (A541, F, F, OMe, 3-isopropyloxybutyl,OCH2), (A542, F, F, OMe, 3-isopropyloxypentyl, OCH2), (A543, F, F, OMe,3-isopropyloxyhexyl, OCH2), (A544, F, F, OMe,3-isopropyloxy-4-methylpentyl, OCH2), (A545, F, F, OMe,3-isopropyloxyheptyl, OCH2), (A546, F, F, OMe,3-isopropyloxy-5-methylhexyl, OCH2), (A547, F, F, OMe,3-isopropyloxy-4,4-dimethylpentyl, OCH2), (A548, F, F, OMe,3-isopropyloxyoctyl, OCH2), (A549, F, F, OMe,3-isopropyloxy-5,5-dimethylhexyl, OCH2), (A550, F, F, OMe,3-n-butyloxypropyl, OCH2), (A551, F, F, OMe, 3-n-butyloxybutyl, OCH2),(A552, F, F, OMe, 3-n-butyloxypentyl, OCH2), (A553, F, F, OMe,3-n-butyloxyhexyl, OCH2), (A554, F, F, OMe, 3-n-butyloxy-4-methylpentyl,OCH2), (A555, F, F, OMe, 3-n-butyloxyheptyl, OCH2), (A556, F, F, OMe,3-n-butyloxy-5-methylhexyl, OCH2), (A557, F, F, OMe,3-n-butyloxy-4,4-dimethylpentyl, OCH2), (A558, F, F, OMe,3-n-butyloxyoctyl, OCH2), (A559, F, F, OMe,3-n-butyloxy-5,5-dimethylhexyl, OCH2), (A560, F, F, OMe,3-isobutyloxypropyl, OCH2), (A561, F, F, OMe, 3-isobutyloxybutyl, CH2),(A562, F, F, OMe, 3-isobutyloxypentyl, OCH2), (A563, F, F, OMe,3-isobutyloxyhexyl, OCH2), (A564, F, F, OMe,3-isobutyloxy-4-methylpentyl, OCH2), (A565, F, F, OMe,3-isobutyloxyheptyl, OCH2), (A566, F, F, OMe,3-isobutyloxy-5-methylhexyl, OCH2), (A567, F, F, OMe,3-isobutyloxy-4,4-dimethylpentyl, OCH2), (A568, F, F, OMe,3-isobutyloxyoctyl, OCH2), (A569, F, F, OMe,3-isobutyloxy-5,5-dimethylhexyl, OCH2), (A570, F, F, OMe,3-t-butyloxypropyl, OCH2), (A571, F, F, OMe, 3-t-butyloxybutyl, OCH2),(A572, F, F, OMe, 3-t-butyloxypentyl, OCH2), (A573, F, F, OMe,3-t-butyloxyhexyl, OCH2), (A574, F, F, OMe, 3-t-butyloxy-4-methylpentyl,OCH2), (A575, F, F, OMe, 3-t-butyloxyheptyl, OCH2), (A576, F, F, OMe,3-t-butyloxy-5-methylhexyl, OCH2), (A577, F, F, OMe,3-t-butyloxy-4,4-dimethylpentyl, OCH2), (A578, F, F, OMe,3-t-butyloxyoctyl, OCH2), (A579, F, F, OMe,3-t-butyloxy-5,5-dimethylhexyl, OCH2), (A580, F, F, OMe,3-n-pentyloxypropyl, OCH2), (A581, F, F, OMe, 3-n-pentyloxybutyl, OCH2),(A582, F, F, OMe, 3-n-pentyloxypentyl, OCH2), (A583, F, F, OMe,3-n-pentyloxyhexyl, OCH2), (A584, F, F, OMe,3-n-pentyloxy-4-methylpentyl, OCH2), (A585, F, F, OMe,3-n-pentyloxyheptyl, OCH2), (A586, F, F, OMe,3-n-pentyloxy-5-methylhexyl, OCH2), (A587, F, F, OMe,3-n-pentyloxy-4,4-dimethylpentyl, OCH2), (A588, F, F, OMe,3-n-pentyloxyoctyl, OCH2), (A589, F, F, OMe,3-n-pentyloxy-5,5-dimethylhexyl, OCH2), (A590, F, F, OMe,3-neopentyloxypropyl, OCH2), (A591, F, F, OMe, 3-neopentyloxybutyl,OCH2), (A592, F, F, OMe, 3-neopentyloxypentyl, OCH2), (A593, F, F, OMe,3-neopentyloxyhexyl, OCH2), (A594, F, F, OMe,3-neopentyloxy-4-methylpentyl, O(CH2), (A595, F, F, OMe,3-neopentyloxyheptyl, OCH2), (A596, F, F, OMe,3-neopentyloxy-5-methylhexyl, OCH2), (A597, F, F, OMe,3-neopentyloxy-4,4-dimethylpentyl, OCH2), (A598, F, F, OMe,3-neopentyloxyoctyl, OCH2), (A599, F, F, OMe,3-neopentyloxy-5,5-dimethylhexyl, OCH2), (A600, Cl, Cl, Me, n-pentyl,CH2CH2), (A602, Cl, Cl, Me, 1-methyloxyethyl, CH2CH2), (A603, Cl, Cl,Me, 1-methyloxypropyl, CH2CH2), (A604, Cl, Cl, Me, 1-methyloxybutyl,CH2CH2), (A605, Cl, Cl, Me, 1-methyloxy-2-methylpropyl, CH2CH2), (A606,Cl, Cl, Me, 1-methyloxypentyl, CH2CH2), (A607, Cl, Cl, Me,1-methyloxy-3-methylbutyl, CH2CH2), (A608, Cl, Cl, Me,1-methyloxy-2,2-dimethylpropyl, CH2CH2), (A609, Cl, Cl, Me,1-methyloxyhexyl, CH2CH2), (A610, Cl, Cl, Me,1-methyloxy-3,3-dimethylbutyl, CH2CH2), (A611, Cl, Cl, Me,1-ethyloxyethyl, CH2CH2), (A612, Cl, Cl, Me, 1-ethyloxypropyl, CH2CH2),(A613, Cl, Cl, Me, 1-ethyloxybutyl, CH2CH2), (A614, Cl, Cl, Me,1-ethyloxy-2-methylpropyl, CH2CH2), (A615, Cl, Cl, Me, 1-ethyloxypentyl,CH2CH2), (A616, Cl, Cl, Me, 1-ethyloxy-3-methylbutyl, CH2CH2), (A617,Cl, Cl, Me, 1-ethyloxy-2,2-dimethylpropyl, CH2CH2), (A618, Cl, Cl, Me,1-ethyloxyhexyl, CH2CH2), (A619, Cl, Cl, Me,1-ethyloxy-3,3-dimethylbutyl, CH2CH2), (A620, Cl, Cl, Me,1-n-propyloxyethyl, CH2CH2), (A621, Cl, Cl, Me, 1-n-propyloxypropyl,CH2CH2), (A622, Cl, Cl, Me, 1-n-propyloxybutyl, CH2CH2), (A623, Cl, Cl,Me, 1-n-propyloxy-2-methylpropyl, CH2CH2), (A624, Cl, Cl, Me,1-n-propyloxypentyl, CH2CH2), (A625, Cl, Cl, Me,1-n-propyloxy-3-methylbutyl, CH2CH2), (A626, Cl, Cl, Me,1-n-propyloxy-2,2-dimethylpropyl, CH2CH2), (A627, Cl, Cl, Me,1-n-propyloxy-n-hexyl, CH2CH2), (A628, Cl, Cl, Me,1-n-propyloxy-3,3-dimethylbutyl, CH2CH2), (A629, Cl, Cl, Me,1-isopropyloxyethyl, CH2CH2), (A630, Cl, Cl, Me, 1-isopropyloxypropyl,CH2CH2), (A631, Cl, Cl, Me, 1-isopropyloxybutyl, CH2CH2), (A-632, Cl,Cl, Me, 1-isopropyloxy-2-methylpropyl, CH2CH2), (A633, Cl, Cl, Me,1-isopropyloxypentyl, CH2CH2), (A634, Cl, Cl, Me,1-isopropyloxy-3-methylbutyl, CH2CH2), (A635, Cl, Cl, Me,1-isopropyloxy-2,2-dimethylpropyl, CH2CH2), (A636, Cl, Cl, Me,1-isopropyloxyhexyl, CH2CH2), (A637, Cl, Cl, Me,1-isopropyloxy-3,3-dimethylbutyl, CH2CH2), (A638, Cl, Cl, Me,1-n-butyloxyethyl, CH2CH2), (A639, Cl, Cl, Me, 1-n-butyloxypropyl,CH2CH2), (A640, Cl, Cl, Me, 1-n-butyloxybutyl, CH2CH2), (A641, Cl, Cl,Me, 1-n-butyloxy-2-methylpropyl, CH2CH2), (A642, Cl, Cl, Me,1-n-butyloxypentyl, CH2CH2), (A643, Cl, Cl, Me,1-n-butyloxy-3-methylbutyl, CH2CH2), (A644, Cl, Cl, Me,1-n-butyloxy-2,2-dimethylpropyl, CH2CH2), (A645, Cl, Cl, Me,1-n-butyloxyhexyl, CH2CH2), (A646, Cl, Cl, Me,1-n-butyloxy-3,3-dimethylbutyl, CH2CH2), (A647, Cl, Cl, Me,1-isobutyloxyethyl, CH2CH2), (A648, Cl, Cl, Me, 1-isobutyloxypropyl,CH2CH2), (A649, Cl, Cl, Me, 1-isobutyloxybutyl, CH2CH2), (A650, Cl, Cl,Me, 1-isobutyloxy-2-methylpropyl, CH2CH2), (A651, Cl, Cl, Me,1-isobutyloxypentyl, CH2CH2), (A652, Cl, Cl, Me,1-isobutyloxy-3-methylbutyl, CH2CH2), (A653, Cl, Cl, Me,1-isobutyloxy-2,2-dimethylpropyl, CH2CH2), (A654, Cl, Cl, Me,1-isobutyloxyhexyl, CH2CH2), (A655, Cl, Cl, Me,1-isobutyloxy-3,3-dimethylbutyl, CH2CH2), (A656, Cl, Cl, Me,1-t-butyloxyethyl CH2CH2), (A657, Cl, Cl, Me, 1-t-butyloxypropyl,CH2CH2), (A658, Cl, Cl, Me, 1-t-butyloxybutyl, CH2CH2), (A659, Cl, Cl,Me, 1-t-butyloxy-2-methylpropyl, CH2CH2), (A660, Cl, Cl, Me,1-t-butyloxypentyl, CH2CH2), (A661, Cl, Cl, Me,1-t-butyloxy-3-methylbutyl, CH2CH2), (A662, Cl, Cl, Me,1-t-butyloxy-2,2-dimethylpropyl, CH2CH2), (A663, Cl, Cl, Me,1-t-butyloxyhexyl, CH2CH2), (A664, Cl, Cl, Me,1-t-butyloxy-3,3-dimethylbutyl, CH2CH2), (A665, Cl, Cl, Me,1-n-pentyloxyethyl, CH2CH2), (A666, Cl, Cl, Me, 1-n-pentyloxypropyl,CH2CH2), (A667, Cl, Cl, Me, 1-n-pentyloxybutyl, CH2CH2), (A668, Cl, Cl,Me, 1-n-pentyloxy-2-methylpropyl, CH2CH2), (A669, Cl, Cl, Me,1-n-pentyloxypentyl, CH2CH2), (A670, Cl, Cl, Me,1-n-pentyloxy-3-methylbutyl, CH2CH2), (A671, Cl, Cl, Me,1-n-pentyloxy-2,2-dimethylpropyl, CH2CH2), (A672, Cl, Cl, Me,1-n-pentyloxyhexyl, CH2CH2), (A673, Cl, Cl, Me,1-n-pentyloxy-3,3-dimethylbutyl, CH2CH2), (A674, G1, Cl, Me,1-neopentyloxyethyl, CH2CH2), (A675, Cl, Cl, Me, 1-neopentyloxypropyl,CH2CH2), (A676, Cl, Cl, Me, 1-neopentyloxybutyl, CH2CH2), (A677, Cl, Cl,Me, 1-neopentyloxy-2-methylpropyl, CH2CH2), (A678, Cl, Cl, Me,1-neopentyloxypentyl, CH2CH2), (A679, Cl, Cl, Me,1-neopentyloxy-3-methylbutyl, CH2CH2), (A680, Cl, Cl, Me,1-neopentyloxy-2,2-dimethylpropyl, CH2CH2), (A681, Cl, Cl, Me,1-neopentyloxyhexyl, CH2CH2), (A682, Cl, Cl, Me,1-neopentyloxy-3,3-dimethylbutyl, CH2CH2), (A683, Cl, Cl, OMe,1-methyloxyethyl, CH2CH2), (A684, Cl, Cl, OMe, 1-methyloxypropyl,CH2CH2), (A685, Cl, Cl, OMe, 1-methyloxybutyl, CH2CH2), (A686, Cl, Cl,OMe, 1-methyloxy-2-methylpropyl, CH2CH2), (A687, Cl, Cl, OMe,1-methyloxypentyl, CH2CH2), (A688, Cl, Cl, OMe,1-methyloxy-3-methylbutyl, CH2CH2), (A689, Cl, Cl, OMe,1-methyloxy-2,2-dimethylpropyl, CH2CH2), (A690, Cl, Cl, OMe,1-methyloxyhexyl, CH2CH2), (A691, Cl, Cl, OMe,1-methyloxy-3,3-dimethylbutyl, CH2CH2), (A692, Cl, Cl, OMe,1-ethyloxyethyl, CH2CH2), (A693, Cl, Cl, OMe, 1-ethyloxypropyl, CH2CH2),(A694, Cl, Cl, OMe, 1-ethyloxybutyl, CH2CH2), (A695, Cl, Cl, OMe,1-ethyloxy-2-methylpropyl, CH2CH2), (A696, Cl, Cl, OMe,1-ethyloxypentyl, CH2CH2), (A697, Cl, Cl, OMe, 1-ethyloxy-3-methylbutyl,CH2CH2), (A698, Cl, Cl, OMe, 1-ethyloxy-2,2-dimethylpropyl, CH2CH2),(A699, Cl, Cl, OMe, 1-ethyloxyhexyl, CH2CH2), (A700, Cl, Cl, OMe,1-ethyloxy-3,3-dimethylbutyl, CH2CH2), (A701, Cl, Cl, OMe,1-n-propyloxyethyl, CH2CH2), (A702, Cl, Cl, OMe, 1-n-propyloxypropyl,CH2CH2), (A703, Cl, Cl, OMe, 1-n-propyloxybutyl, CH2 CH2), (A704, Cl,Cl, OMe, 1-n-propyloxy-2-methylpropyl, CH2CH2), (A705, Cl, Cl, OMe,1-n-propyloxypentyl, CH2CH2), (A706, Cl, Cl, OMe,1-n-propyloxy-3-methylbutyl, CH2CH2), (A707, Cl, Cl, OMe,1-n-propyloxy-2,2-dimethylpropyl, CH2CH2), (A708, Cl, Cl, OMe,1-n-propyloxy-n-hexyl, CH2CH2), (A709, Cl, Cl, OMe,1-n-propyloxy-3,3-dimethylbutyl, CH2CH2), (A710, Cl, Cl, OMe,1-isopropyloxyethyl, CH2CH2), (A711, Cl, Cl, OMe, 1-isopropyloxypropyl,CH2CH2), (A712, Cl, Cl, OMe, 1-isopropyloxybutyl, CH2CH2), (A713, Cl,Cl, OMe, 1-isopropyloxy-2-methylpropyl, CH2CH2), (A714, Cl, Cl, OMe,1-isopropyloxypentyl, CH2CH2), (A715, Cl, Cl, OMe,1-isopropyloxy-3-methylbutyl, CH2CH2), (A716, Cl, Cl, OMe,1-isopropyloxy-2,2-dimethylpropyl, CH2CH2), (A717, Cl, Cl, OMe,1-isopropyloxyhexyl, CH2CH2), (A718, Cl, Cl, OMe,1-isopropyloxy-3,3-dimethylbutyl, CH2CH2), (A719, Cl, Cl, OMe,1-n-butyloxyethyl, CH2CH2), (A720, Cl, Cl, OMe, 1-n-butyloxypropyl,CH2CH2), (A721, Cl, Cl, OMe, 1-n-butyloxybutyl, CH2CH2), (A722, Cl, Cl,OMe, 1-n-butyloxy-2-methylpropyl, CH2CH2), (A723, Cl, Cl, OMe,1-n-butyloxypentyl, CH2CH2), (A724, Cl, Cl, OMe,1-n-butyloxy-3-methylbutyl, CH2CH2), (A725, Cl, Cl, OMe,1-n-butyloxy-2,2-dimethylpropyl, CH2CH2), (A726, Cl, Cl, OMe,1-n-butyloxyhexyl, CH2CH2), (A727, Cl, Cl, OMe,1-n-butyloxy-3,3-dimethylbutyl, CH2CH2), (A728, Cl, Cl, OMe,1-isobutyloxyethyl, CH2CH2), (A729, Cl, Cl, OMe, 1-isobutyloxypropyl,CH2CH2), (A730, Cl, Cl, OMe, 1-isobutyloxybutyl, CH2CH2), (A731, Cl, Cl,OMe, 1-isobutyloxy-2-methylpropyl, CH2CH2), (A732, Cl, Cl, OMe,1-isobutyloxypentyl, CH2CH2), (A733, Cl, Cl, OMe,1-isobutyloxy-3-methylbutyl, CH2CH2), (A734, Cl, Cl, OMe,1-isobutyloxy-2,2-dimethylpropyl, CH2CH2), (A735, Cl, Cl, OMe,1-isobutyloxyhexyl, CH2CH2), (A736, Cl, Cl, OMe,1-isobutyloxy-3,3-dimethylbutyl, CH2CH2), (A737, Cl, Cl, OMe,1-t-butyloxyethyl, CH2CH2), (A738; Cl, Cl, OMe, 1-t-butyloxypropyl,CH2CH2), (A739, Cl, Cl, OMe, 1-t-butyloxybutyl, CH2CH2), (A740, Cl, Cl,OMe, 1-t-butyloxy-2-methylpropyl, CH2CH2), (A741, Cl, Cl, OMe,1-t-butyloxypentyl, CH2CH2), (A742, Cl, Cl, OMe,1-t-butyloxy-3-methylbutyl, CH2CH2), (A743, Cl, Cl, OMe,1-t-butyloxy-2,2-dimethylpropyl, CH2CH2), (A744, Cl, Cl, OMe,1-t-butyloxyhexyl, CH2CH2), (A745, Cl, Cl, OMe,1-t-butyloxy-3,3-dimethylbutyl, CH2CH2), (A746, Cl, Cl, OMe,1-n-pentyloxyethyl, CH2CH2), (A747, Cl, Cl, OMe, 1-n-pentyloxypropyl,CH2CH2), (A748, Cl, Cl, OMe, 1-n-pentyloxybutyl, CH2CH2), (A749, Cl, Cl,OMe, 1-n-pentyloxy-2-methylpropyl, CH2CH2), (A750, Cl, Cl, OMe,1-n-pentyloxypentyl, CH2CH2), (A751, Cl, Cl, OMe,1-n-pentyloxy-3-methylbutyl, CH2CH2), (A752, Cl, Cl, OMe,1-n-pentyloxy-2,2-dimethylpropyl, CH2CH2), (A753, Cl, Cl, OMe,1-n-pentyloxyhexyl, CH2CH2), (A754, Cl, Cl, OMe,1-n-pentyloxy-3,3-dimethylbutyl, CH2CH2), (A755, Cl, Cl, OMe,1-neopentyloxyethyl, CH2CH2), (A756, Cl, Cl, OMe, 1-neopentyloxypropyl,CH2CH2), (A757, Cl, G1, OMe, 1-neopentyloxybutyl, CH2CH2), (A758, Cl,Cl, OMe, 1-neopentyloxy-2-methylpropyl, CH2CH2), (A759, Cl, Cl, OMe,1-neopentyloxypentyl, CH2CH2), (A760, Cl, Cl, OMe,1-neopentyloxy-3-methylbutyl, CH2CH2), (A761, Cl, Cl, OMe,1-neopentyloxy-2,2-dimethylpropyl, CH2CH2), (A762, Cl, Cl, OMe,1-neopentyloxyhexyl, CH2CH2), (A763, Cl, Cl, OMe,1-neopentyloxy-3,3-dimethylbutyl, CH2CH2), (A764, Cl, Cl, Me,1-methyloxyethyl, OCH2), (A765, Cl, Cl, Me, 1-methyloxypropyl, OCH2),(A766, Cl, Cl, Me, 1-methyloxybutyl, OCH2), (A767, Cl, Cl, Me,1-methyloxy-2-methylpropyl, OCH2), (A768, Cl, Cl, Me, 1-methyloxypentyl,OCH2), (A769, Cl, Cl, Me, 1-methyloxy-3-methylbutyl, OCH2), (A770, Cl,Cl, Me, 1-methyloxy-2,2-dimethylpropyl, OCH2), (A771, Cl, Cl, Me,1-methyloxyhexyl, OCH2), (A772, Cl, Cl, Me,1-methyloxy-3,3-dimethylbutyl, OCH2), (A773, Cl, Cl, Me,1-ethyloxyethyl, OCH2), (A774, Cl, Cl, Me, 1-ethyloxypropyl, OCH2),(A775, Cl, Cl, Me, 1-ethyloxybutyl, OCH2), (A776, Cl, Cl, Me,1-ethyloxy-2-methylpropyl, OCH2), (A777, Cl, Cl, Me, 1-ethyloxypentyl,OCH2), (A778, Cl, Cl, Me, 1-ethyloxy-3-methylbutyl, OCH2), (A779, Cl,Cl, Me, 1-ethyloxy-2,2-dimethylpropyl, OCH2), (A780, Cl, Cl, Me,1-ethyloxyhexyl, OCH2), (A781, Cl, Cl, Me, 1-ethyloxy-3,3-dimethylbutyl,OCH2), (A782, Cl, Cl, Me, 1-n-propyloxyethyl, OCH2), (A783, Cl, Cl, Me,1-n-propyloxypropyl, OCH2), (A784, Cl, Cl, Me, 1-n-propyloxybutyl,OCH2), (A785, Cl, Cl, Me, 1-n-propyloxy-2-methylpropyl, OCH2), (A786,Cl, Cl, Me, 1-n-propyloxypentyl, OCH2), (A787, Cl, Cl, Me,1-n-propyloxy-3-methylbutyl, OCH2), (A788, Cl, Cl, Me,1-n-propyloxy-2,2-dimethylpropyl, OCH2), (A789, Cl, Cl, Me,1-n-propyloxyhexyl, OCH2), (A790, Cl, Cl, Me,1-n-propyloxy-3,3-dimethylbutyl, OCH2), (A791, Cl, Cl, Me,1-isopropyloxyethyl, OCH2), (A792, Cl, Cl, Me, 1-isopropyloxypropyl,OCH2), (A793, Cl, Cl, Me, 1-isopropyloxybutyl, OCH2), (A794, Cl, Cl, Me,1-isopropyloxy-2-methylpropyl, OCH2), (A795, Cl, Cl, Me,1-isopropyloxypentyl, OCH2), (A796, Cl, Cl, Me,1-isopropyloxy-3-methylbutyl, OCH2), (A797, Cl, Cl, Me,1-isopropyloxy-2,2-dimethylpropyl, OCH2), (A798, Cl, Cl, Me,1-isopropyloxyhexyl, OCH2), (A799, Cl, Cl, Me,1-isopropyloxy-3,3-dimethylbutyl, OCH2), (A800, Cl, Cl, Me,1-n-butyloxyethyl, OCH2), (A801, Cl, Cl, Me, 1-n-butyloxypropyl, OCH2),(A802, Cl, Cl, Me, 1-n-butyloxybutyl, OCH2), (A803, Cl, Cl, Me,1-n-butyloxy-2-methylpropyl, OCH2), (A804, Cl, Cl, Me,1-n-butyloxypentyl, OCH2), (A805, Cl, Cl, Me,1-n-butyloxy-3-methylbutyl, OCH2), (A806, Cl, Cl, Me,1-n-butyloxy-2,2-dimethylpropyl, OCH2), (A807, Cl, Cl, Me,1-n-butyloxyhexyl, OCH2), (A808, Cl, Cl, Me,1-n-butyloxy-3,3-dimethylbutyl, OCH2), (A809, Cl, Cl, Me,1-isobutyloxyethyl, OCH2), (A810, Cl, Cl, Me, 1-isobutyloxypropyl,OCH2), (A811, Cl, Cl, Me, 1-isobutyloxybutyl, OCH2), (A812, Cl, Cl, Me,1-isobutyloxy-2-methylpropyl, OCH2), (A813, Cl, Cl, Me,1-isobutyloxypentyl, OCH2), (A814, Cl, Cl, Me,1-isobutyloxy-3-methylbutyl, OCH2), (A815, Cl, Cl, Me,1-isobutyloxy-2,2-dimethylpropyl, OCH2), (A816, Cl, Cl, Me,1-isobutyloxyhexyl, OCH2), (A817, Cl, Cl, Me,1-isobutyloxy-3,3-dimethylbutyl, OCH2), (A818, Cl, Cl, Me,1-t-butyloxyethyl, OCH2), (A819, Cl, Cl, Me, 1-t-butyloxypropyl, OCH2),(A820, Cl, Cl, Me, 1-t-butyloxybutyl, OCH2), (A821, Cl, Cl, Me,1-t-butyloxy-2-methylpropyl, OCH2), (A822, Cl, Cl, Me,1-t-butyloxypentyl, OCH2), (A823, Cl, Cl, Me,1-t-butyloxy-3-methylbutyl, OCH2), (A824, Cl, Cl, Me,1-t-butyloxy-2,2-dimethylpropyl, OCH2), (A825, Cl, Cl, Me,1-t-butyloxyhexyl, OCH2), (A826, Cl, Cl, Me,1-t-butyloxy-3,3-dimethylbutyl, OCH2), (A827, Cl, Cl, Me,1-n-pentyloxyethyl, OCH2), (A828, Cl, Cl, Me, 1-n-pentyloxypropyl,OCH2), (A829, Cl, Cl, Me, 1-n-pentyloxybutyl, OCH2), (A830, Cl, Cl, Me,1-n-pentyloxy-2-methylpropyl, OCH2), (A831, Cl, Cl, Me,1-n-pentyloxypentyl, OCH2), (A832, Cl, Cl, Me,1-n-pentyloxy-3-methylbutyl, OCH2), (A833, Cl, Cl, Me,1-n-pentyloxy-2,2-dimethylpropyl, OCH2), (A834, Cl, Cl, Me,1-n-pentyloxyhexyl, OCH2), (A835, Cl, Cl, Me,1-n-pentyloxy-3,3-dimethylbutyl, OCH2), (A836, Cl, Cl, Me,1-neopentyloxyethyl, OCH2), (A837, Cl, Cl, Me, 1-neopentyloxypropyl,OCH2), (A838, Cl, Cl, Me, 1-neopentyloxybutyl, OCH2), (A839, Cl, Cl, Me,1-neopentyloxy-2-methylpropyl, OCH2), (A840, Cl, Cl, Me,1-neopentyloxypentyl, OCH2), (A841, Cl, Cl, Me,1-neopentyloxy-3-methylbutyl, OCH2), (A842, Cl, Cl, Me,1-neopentyloxy-2,2-dimethylpropyl, OCH2), (A843, Cl, Cl, Me,1-neopentyloxyhexyl, OCH2), (A844, Cl, Cl, Me,1-neopentyloxy-3,3-dimethylbutyl, OCH2), (A845, Cl, Cl, OMe,1-methyloxyethyl, OCH2), (A846, Cl, Cl, OMe, 1-methyloxypropyl, OCH2),(A847, Cl, Cl, OMe, 1-methyloxybutyl, OCH2), (A848, Cl, Cl, OMe,1-methyloxy-2-methylpropyl, OCH2), (A849, Cl, Cl, OMe,1-methyloxypentyl, OCH2), (A850, Cl, Cl, OMe, 1-methyloxy-3-methylbutyl,OCH2), (A851, Cl, Cl, OMe, 1-methyloxy-2,2-dimethylpropyl, OCH2), (A852,Cl, Cl, OMe, 1-methyloxyhexyl, OCH2), (A853, Cl, Cl, OMe,1-methyloxy-3,3-dimethylbutyl, OCH2), (A854, Cl, Cl, OMe,1-ethyloxyethyl, OCH2), (A855, Cl, Cl, OMe, 1-ethyloxypropyl, OCH2),(A856, Cl, Cl, OMe, 1-ethyloxybutyl, OCH2), (A857, Cl, Cl, OMe,1-ethyloxy-2-methylpropyl, OCH2), (A858, Cl, Cl, OMe, 1-ethyloxypentyl,OCH2), (A859, Cl, Cl, OMe, 1-ethyloxy-3-methylbutyl, OCH2), (A860, Cl,Cl, OMe, 1-ethyloxy-2,2-dimethylpropyl, OCH2), (A861, Cl, Cl, OMe,1-ethyloxyhexyl, OCH2), (A862, Cl, Cl, OMe,1-ethyloxy-3,3-dimethylbutyl, OCH2), (A863, Cl, Cl, OMe,1-n-propyloxyethyl, OCH2), (A864, Cl, Cl, OMe, 1-n-propyloxypropyl,OCH2), (A865, Cl, Cl, OMe, 1-n-propyloxybutyl, OCH2), (A868, Cl, Cl,OMe, 1-n-propyloxy-2-methylpropyl, OCH2), (A867, Cl, Cl, OMe,1-n-propyloxypentyl, OCH2), (A868, Cl, Cl, OMe,1-n-propyloxy-3-methylbutyl, OCH2), (A869, Cl, Cl, OMe,1-n-propyloxy-2,2-dimethylpropyl, OCH2), (A870, Cl, Cl, OMe,1-n-propyloxyhexyl, OCH2), (A871, Cl, Cl, OMe,1-n-propyloxy-3,3-dimethylbutyl, OCH2), (A872, Cl, Cl, OMe,1-isopropyloxyethyl, OCH2), (A873, Cl, Cl, OMe, 1-isopropyloxypropyl,OCH2), (A874, Cl, Cl, OMe, 1-isopropyloxybutyl, OCH2), (A875, Cl, Cl,OMe, 1-isopropyloxy-2-methylpropyl, OCH2), (A876, Cl, Cl, OMe,1-isopropyloxypentyl, OCH2), (A877, Cl, Cl, OMe,1-isopropyloxy-3-methylbutyl, OCH2), (A878, Cl, Cl, OMe,1-isopropyloxy-2,2-dimethylpropyl, OCH2), (A879, Cl, Cl, OMe,1-isopropyloxyhexyl, OCH2), (A880, Cl, Cl, OMe,1-isopropyloxy-3,3-dimethylbutyl, OCH2), (A881, Cl, Cl, OMe,1-n-butyloxyethyl, OCH2), (A882, Cl, Cl, OMe, 1-n-butyloxypropyl, OCH2),(A883, Cl, Cl, OMe, 1-n-butyloxybutyl, OCH2), (A884, Cl, Cl, OMe,1-n-butyloxy-2-methylpropyl, OCH2), (A885, Cl, Cl, OMe,1-n-butyloxypentyl, OCH2), (A886, Cl, Cl, OMe,1-n-butyloxy-3-methylbutyl, OCH2), (A887, Cl, Cl, OMe,1-n-butyloxy-2,2-dimethylpropyl, OCH2), (A888, Cl, Cl, OMe,1-n-butyloxyhexyl, OCH2), (A889, Cl, Cl, OMe,1-n-butyloxy-3,3-dimethylbutyl, OCH2), (A890, Cl, Cl, OMe,1-isobutyloxyethyl, OCH2), (A891, Cl, Cl, OMe, 1-isobutyloxypropyl,OCH2), (A892, Cl, Cl, OMe, 1-isobutyloxybutyl, OCH2), (A893, Cl, Cl,OMe, 1-isobutyloxy-2-methylpropyl, OCH2), (A894, Cl, Cl, OMe,1-isobutyloxypentyl, OCH2), (A895, Cl, Cl, OMe,1-isobutyloxy-3-methylbutyl, OCH2), (A896, Cl, Cl, OMe,1-isobutyloxy-2,2-dimethylpropyl, OCH2), (A897, Cl, Cl, OMe,1-isobutyloxyhexyl, OCH2), (A898, Cl, Cl, OMe,1-isobutyloxy-3,3-dimethylbutyl, OCH2), (A899, Cl, Cl, OMe,1-t-butyloxyethyl, OCH2), (900, Cl, Cl, OMe, 1-t-butyloxypropyl, OCH2),(A901, Cl, Cl, OMe, 1-t-butyloxybutyl, OCH2), (A902, Cl, Cl, OMe,1-t-butyloxy-2-methylpropyl, OCH2), (A903, Cl, Cl, OMe,1-t-butyloxypentyl, OCH2), (A904, Cl, Cl, OMe,1-t-butyloxy-3-methylbutyl, OCH2), (A905, Cl, Cl, OMe,1-t-butyloxy-2,2-dimethylpropyl, OCH2), (A906, Cl, Cl, OMe,1-t-butyloxyhexyl, OCH2), (A907, Cl, Cl, OMe,1-t-butyloxy-3,3-dimethylbutyl, OCH2), (A908, Cl, Cl, OMe,1-n-pentyloxyethyl, OCH2), (A909, Cl, Cl, OMe, 1-n-pentyloxypropyl,OCH2), (A910, Cl, Cl, OMe, 1-n-pentyloxybutyl, OCH2), (A911, Cl, Cl,OMe, 1-n-pentyloxy-2-methylpropyl, OCH2), (A912, Cl, Cl, OMe,1-n-pentyloxypentyl, OCH2), (A913, Cl, Cl, OMe,1-n-pentyloxy-3-methylbutyl, OCH2), (A914, Cl, Cl, OMe,1-n-pentyloxy-2,2-dimethylpropyl, 9CH2), (A915, Cl, Cl, OMe,1-n-pentyloxyhexyl, OCH2), (A916, Cl, Cl, OMe,1-n-pentyloxy-3,3-dimethylbutyl, OCH2), (A917, Cl, Cl, OMe,1-neopentyloxyethyl, OCH2), (A918, Cl, Cl, OMe, 1-neopentyloxypropyl,OCH2), (A919, Cl, Cl, OMe, 1-neopentyloxybutyl, OCH2), (A920, Cl, Cl,OMe, 1-neopentyloxy-2-methylpropyl, OCH2), (A921, Cl, Cl, OMe,1-neopentyloxypentyl, OCH2), (A922, Cl, Cl, OMe,1-neopentyloxy-3-methylbutyl, OCH2), (A923, Cl, Cl, OMe,1-neopentyloxy-2,2-dimethylpropyl, OCH2), (A924, Cl, Cl, OMe,1-neopentyloxyhexyl, OCH2), (A925, Cl, Cl, OMe,1-neopentyloxy-3,3-dimethylbutyl, OCH2), (A926, Cl, Cl, Me,3-methyloxypropyl, CH2CH2), (A927, Cl, Cl, Me, 3-methyloxybutyl,CH2CH2), (A929, Cl, Cl, Me, 3-methyloxy-4-methylpentyl, CH2CH2), (A931,Cl, Cl, Me, 3-methyloxy-5-methylhexyl, CH2CH2), (A933, Cl, Cl, Me,3-methyloxyoctyl, CH2CH2), (A934, Cl, Cl, Me,3-methyloxy-5,5-dimethylhexyl, CH2CH2), (A935, Cl, Cl, Me,3-ethyloxybutyl, CH2CH2), (A938, Cl, Cl, Me, 3-ethyloxy-4-methylpentyl,CH2CH2), (A940, Cl, Cl, Me, 3-ethyloxy-5-methylhexyl, CH2CH2), (A942,Cl, Cl, Me, 3-ethyloxyoctyl, CH2C1H₂), (A943, Cl, Cl, Me,3-ethyloxy-5,5-dimethylhexyl, CH2CH2), (A945, Cl, Cl, Me,3-n-propyloxybutyl, CH2CH2), (A946, Cl, Cl, Me, 3-n-propyloxypentyl,CH2CH2), (A947, Cl, Cl, Me, 3-n-propyloxyhexyl, CH2CH2), (A948, Cl, Cl,Me, 3-n-propyloxy-4-methylpentyl, CH2CH2), (A949, Cl, Cl, Me,3-n-propyloxyheptyl, CH2CH2), (A950, Cl, Cl, Me,3-n-propyloxy-5-methylhexyl, CH2CH2), (A951, Cl, Cl, Me,3-n-propyloxy-4,4-dimethylpentyl, CH2CH2), (A952, Cl, Cl, Me,3-n-propyloxyoctyl, CH2CH2), (A953, Cl, Cl, Me,3-n-propyloxy-5,5-dimethylhexyl, CH2CH2), (A955, Cl, Cl, Me,3-isopropyloxybutyl, CH2CH2), (A956, Cl, Cl, Me, 3-isopropyloxypentyl,CH2CH2), (A957, Cl, Cl, Me, 3-isopropyloxyhexyl, CH2CH2), (A958, Cl, Cl,Me, 3-isopropyloxy-4-methylpentyl, CH2CH2), (A959, Cl, Cl, Me,3-isopropyloxyheptyl, CH2CH2), (A960, Cl, Cl, Me,3-isopropyloxy-5-methylhexyl, CH2CH2), (A961, Cl, Cl, Me,3-isopropyloxy-4,4-dimethylpentyl, CH2CH2), (A962, Cl, Cl, Me,3-isopropyloxyoctyl, CH2CH2), (A963, Cl, Cl, Me,3-isopropyloxy-5,5-dimethylhexyl, CH2CH2), (A964, Cl, Cl, Me,3-n-butyloxybutyl, CH2CH2), (A965, Cl, Cl, Me, 3-n-butyloxypentyl,CH2CH2), (A966, Cl, Cl, Me, 3-n-butyloxyhexyl, CH2CH2), (A967, Cl, Cl,Me, 3-n-butyloxy-4-methylpentyl, CH2CH2), (A968, Cl, Cl, Me,3-n-butyloxyheptyl, CH2CH2), (A969, Cl, Cl, Me,3-n-butyloxy-5-methylhexyl, CH2CH2), (A970, Cl, Cl, Me,3-n-butyloxy-4,4-dimethylpentyl, CH2CH2), (A971, Cl, Cl, Me,3-n-butyloxyoctyl, CH2CH2), (A972, Cl, Cl, Me,3-n-butyloxy-5,5-dimethylhexyl, CH2CH2), (A973, Cl, Cl, Me,3-isobutyloxypropyl, CH2CH2), (A974, Cl, Cl, Me, 3-isobutyloxybutyl,CH2CH2), (A975, Cl, Cl, Me, 3-isobutyloxypentyl, CH2CH2), (A976, Cl, Cl,Me, 3-isobutyloxyhexyl, CH2CH2), (A977, Cl, Cl, Me,3-isobutyloxy-4-methylpentyl, CH2CH2), (A978, Cl, Cl, Me,3-isobutyloxyheptyl, CH2CH2), (A979, Cl, Cl, Me,3-isobutyloxy-5-methylhexyl, CH2CH2), (A980, Cl, Cl, Me,3-isobutyloxy-4,4-dimethylpentyl, CH2CH2), (A981, Cl, Cl, Me,3-isobutyloxyoctyl, CH2CH2), (A982, Cl, Cl, Me,3-isobutyloxy-5,5-dimethylhexyl, CH2CH2), (A983, Cl, Cl, Me,3-t-butyloxypropyl, CH2CH2), (A984, Cl, Cl, Me, 3-t-butyloxybutyl,CH2CH2), (A985, Cl, Cl, Me, 3-t-butyloxypentyl, CH2CH2), (A986, Cl, Cl,Me, 3-t-butyloxyhexyl, CH2CH2), (A987, Cl, Cl, Me,3-t-butyloxy-4-methylpentyl, CH2CH2), (A988, Cl, Cl, Me,3-t-butyloxyheptyl, CH2CH2), (A989, Cl, Cl, Me,3-t-butyloxy-5-methylhexyl, CH2CH2), (A990, Cl, Cl, Me,3-t-butyloxy-4,4-dimethylpentyl, CH2CH2), (A991, Cl, Cl, Me,3-t-butyloxyoctyl, CH2CH2), (A992, Cl, Cl, Me,3-t-butyloxy-5,5-dimethylhexyl, CH2CH2), (A994, Cl, Cl, Me,3-n-pentyloxybutyl, CH2CH2), (A995, Cl, Cl, Me, 3-n-pentyloxypentyl,CH2CH2), (A996, Cl, Cl, Me, 3-n-pentyloxyhexyl, CH2CH2), (A997, Cl, Cl,Me, 3-n-pentyloxy-4-methylpentyl, CH2CH2), (A998, Cl, Cl; Me,3-n-pentyloxyheptyl, CH2CH2), (A999, Cl, Cl, Me,3-n-pentyloxy-5-methylhexyl, CH2CH2), (A1000, Cl, Cl, Me,3-n-pentyloxy-4,4-dimethylpentyl, CH2CH2), (A1001, Cl, Cl, Me,3-n-pentyloxyoctyl, CH2CH2), (A1002, Cl, Cl, Me,3-n-pentyloxy-5,5-dimethylhexyl, CH2CH2), (A1004, Cl, Cl, Me,3-neopentyloxybutyl, CH2CH2), (A1005, Cl, Cl, Me, 3-neopentyloxypentyl,CH2CH2), (A1006, Cl, Cl, Me, 3-n-neopentyloxyhexyl, CH2CH2), (A1007, Cl,Cl, Me, 3-neopentyloxy-4-methylpentyl, CH2CH2), (A1008, Cl, Cl, Me,3-neopentyloxyheptyl, CH2CH2), (A1009, Cl, Cl, Me,3-neopentyloxy-5-methylhexyl, CH2CH2), (A1010, Cl, Cl, Me,3-neopentyloxy-4,4-dimethylpentyl, CH2CH2), (A1011, Cl, Cl, Me,3-neopentyloxyoctyl, CH2CH2), (A1012, Cl, Cl, Me,3-neopentyloxy-5,5-dimethylhexyl, CH2CH2), (A1013, Cl, Cl, OMe,3-methyloxypropyl, CH2CH2), (A1014, Cl, Cl, OMe, 3-methyloxybutyl,CH2CH2), (A1015, Cl, Cl, OMe, 3-methyloxypentyl, CH2CH2), (A1017, Cl,Cl, OMe, 3-methyloxy-4-methylpentyl, CH2CH2), (A1019, Cl, Cl, OMe,3-methyloxy-5-methylhexyl, CH2CH2), (A1020, Cl, Cl, OMe,3-methoxy-4,4-dimethylpentyl, CH2CH2), (A1021, Cl, Cl, OMe,3-methyloxyoctyl, CH2CH2), (A1022, Cl, Cl, OMe,3-methyloxy-5,5-dimethylhexyl, CH2CH2), (A1023, Cl, Cl, OMe,3-ethyloxypropyl, CH2CH2), (A1024, Cl, Cl, OMe, 3-ethyloxybutyl,CH2CH2), (A1025, Cl, Cl, OMe, 3-ethyloxypentyl, CH2CH2), (A1026, Cl, Cl,OMe, 3-ethyloxyhexyl, CH2CH2), (A1027, Cl, Cl, OMe,3-ethyloxy-4-methylpentyl, CH2CH2), (A1028, Cl, Cl, OMe,3-ethyloxyheptyl, CH2CH2), (A1029, Cl, Cl, OMe,3-ethyloxy-5-methylhexyl, CH2CH2), (A1030, Cl, Cl, OMe,3-ethoxy-4,4-dimethylpentyl, CH2CH2), (A1031, Cl, Cl, OMe,3-ethyloxyoctyl, CH2CH2), (A1032, Cl, Cl, OMe,3-ethyloxy-5,5-dimethylhexyl, CH2CH2), (A1034, Cl, Cl, OMe,3-n-propyloxybutyl, CH2CH2), (A1035, Cl, Cl, OMe, 3-n-propyloxypentyl,CH2CH2), (A1036, Cl, Cl, OMe, 3-n-propyloxyhexyl, CH2CH2), (A1037, Cl,Cl, OMe, 3-n-propyloxy-4-methylpentyl, CH2CH2), (A1038, Cl, Cl, OMe,3-n-propyloxyheptyl, CH2CH2), (A1039, Cl, Cl, OMe,3-n-propyloxy-5-methylhexyl, CH2CH2), (A1040, Cl, Cl, OMe,3-n-propyloxy-4,4-dimethylpentyl, CH2CH2), (A1041, Cl, Cl, OMe,3-n-propyloxyoctyl, CH2CH2), (A1042, Cl, Cl, OMe,3-n-propyloxy-5,5-dimethylhexyl, CH2CH2), (A1043, Cl, Cl, OMe,3-isopropyloxypropyl, CH2CH2), (A1044, Cl, Cl, OMe, 3-isopropyloxybutyl,CH2CH2), (A1045, Cl, Cl, OMe, 3-isopropyloxypentyl, CH2CH2), (A1046, Cl,Cl, OMe, 3-isopropyloxyhexyl, CH2CH2), (A1047, Cl, Cl, OMe,3-isopropyloxy-4-methylpentyl, CH2CH2), (A1048, Cl, Cl, OMe,3-isopropyloxyheptyl, CH2CH2), (A1049, Cl, Cl, OMe,3-isopropyloxy-5-methylhexyl, CH2CH2), (A1050, Cl, Cl, OMe,3-isopropyloxy-4,4-dimethylpentyl, CH2CH2), (A1051, Cl, Cl, OMe,3-isopropyloxyoctyl, CH2CH2), (A1052, Cl, Cl, OMe,3-isopropyloxy-5,5-dimethylhexyl, CH2CH2), (A1053, Cl, Cl, OMe,3-n-butyloxypropyl, CH2CH2), (A1054, Cl, Cl, OMe, 3-n-butyloxybutyl,CH2CH2), (A1055, Cl, Cl, OMe, 3-n-butyloxypentyl, CH2CH2), (A1056, Cl,Cl, OMe, 3-n-butyloxyhexyl, CH2CH2), (A1057, Cl, Cl, OMe,3-n-butyloxy-4-methylpentyl, CH2CH2), (A1058, Cl, Cl, OMe,3-n-butyloxyheptyl, CH2CH2), (A1059, Cl, Cl, OMe,3-n-butyloxy-5-methylhexyl, CH2CH2), (A1060, Cl, Cl, OMe,3-n-butyloxy-4,4-dimethylpentyl, CH2CH2), (A1061, Cl, Cl, OMe,3-n-butyloxyoctyl, CH2CH2), (A1062, Cl, Cl, OMe,3-n-butyloxy-5,5-dimethylhexyl, CH2CH2), (A1063, Cl, Cl, OMe,3-isobutyloxypropyl, CH2CH2), (A1064, Cl, Cl, OMe, 3-isobutyloxybutyl,CH2CH2), (A1065, Cl, Cl, OMe, 3-isobutyloxypentyl, CH2CH2), (A1066, Cl,Cl, OMe, 3-isobutyloxyhexyl, CH2CH2), (A1067, Cl, Cl, OMe,3-isobutyloxy-4-methylpentyl, CH2CH2), (A1068, Cl, Cl, OMe,3-isobutyloxyheptyl, CH2CH2), (A1069, Cl, Cl, OMe,3-isobutyloxy-5-methylhexyl, CH2CH2), (A1070, Cl, Cl, OMe,3-isobutyloxy-4,4-dimethylpentyl, CH2CH2), (A1071, Cl, Cl, OMe,3-isobutyloxyoctyl, CH2CH2), (A1072, Cl, Cl, OMe,3-isobutyloxy-5,5-dimethylhexyl, CH2CH2), (A1073, Cl, Cl, OMe,3-t-butyloxypropyl, CH2CH2), (A1074, Cl, Cl, OMe, 3-t-butyloxybutyl,CH2CH2), (A1075, Cl, Cl, OMe, 3-t-butyloxypentyl, CH2CH2), (A1076, Cl,Cl, OMe, 3-t-butyloxyhexyl, CH2CH2), (A1077, Cl, Cl, OMe,3-t-butyloxy-4-methylpentyl, CH2CH2), (A1078, Cl, Cl, OMe,3-t-butyloxyheptyl, CH2CH2), (A1079, Cl, Cl, OMe,3-t-butyloxy-5-methylhexyl, CH2CH2), (A1080, Cl, Cl, OMe,3-t-butyloxy-4,4-dimethylpentyl, CH2CH2), (A1081, Cl, Cl, OMe,3-t-butyloxyoctyl, CH2CH2), (A1082, Cl, Cl, OMe,3-t-butyloxy-5,5-dimethylhexyl, CH2CH2), (A1083, Cl, Cl, OMe,3-n-pentyloxypropyl, CH2CH2), (A1084, Cl, Cl, OMe, 3-n-pentyloxybutyl,CH2CH2), (A1085, Cl, Cl, OMe, 3-n-pentyloxypentyl, CH2CH2), (A1086, Cl,Cl, OMe, 3-n-pentyloxyhexyl, CH2CH2), (A1087, Cl, Cl, OMe,3-n-pentyloxy-4-methylpentyl, CH2CH2), (A1088, Cl, Cl, OMe,3-n-pentyloxyheptyl, CH2CH2), (A1089, Cl, Cl, OMe,3-n-pentyloxy-5-methylhexyl, CH2CH2), (A1090, Cl, Cl, OMe,3-n-pentyloxy-4,4-dimethylpentyl, CH2CH2), (A1091, Cl, Cl, OMe,3-n-pentyloxyoctyl, CH2CH2), (A1092, Cl, Cl, OMe,3-n-pentyloxy-5,5-dimethylhexyl, CH2CH2), (A1093, Cl, Cl, OMe,3-neopentyloxypropyl, CH2CH2), (A1094, Cl, Cl, OMe, 3-neopentyloxybutyl,CH2CH2), (A1095, Cl, Cl, OMe, 3-neopentyloxypentyl, CH2CH2), (A1096, Cl,Cl, OMe, 3-neopentyloxyhexyl, CH2CH2), (A1097, Cl, Cl, OMe,3-neopentyloxy-4-methylpentyl, CH2CH2), (A1098, Cl, Cl, OMe,3-neopentyloxyheptyl, CH2CH2), (A1099, Cl, Cl, OMe,3-neopentyloxy-5-methylhexyl, CH2CH2), (A1100, Cl, Cl, OMe,3-neopentyloxy-4,4-dimethylpentyl, CH2CH2), (A1101, Cl, Cl, OMe,3-neopentyloxyoctyl, CH2CH2), (A1102, Cl, Cl, OMe,3-neopentyloxy-5,5-dimethylhexyl, CH2CH2), (A1103, Cl, —Cl, Me,3-methyloxypropyl, OCH2), (A1104, Cl, Cl, Me, 3-methyloxybutyl, OCH2),(A1105, Cl, Cl, Me, 3-methyloxypentyl, OCH2), (A1106, Cl, Cl, Me,3-methyloxyhexyl, OCH2), (A1107, Cl, Cl, Me, 3-methyloxy-4-methylpentyl,OCH2), (A1108, Cl, Cl, Me, 3-methyloxyheptyl, OCH2), (A1109, Cl, Cl, Me,3-methyloxy-5-methylhexyl, OCH2), (A110, Cl, Cl, Me,3-methoxy-4,4-dimethylpentyl, OCH2), (A1111, Cl, Cl, Me,3-methyloxyoctyl, OCH2), (A1112, Cl, Cl, Me,3-methyloxy-5-dimethylhexyl, OCH2), (A1113, Cl, Cl, Me,3-ethyloxypropyl, OCH2), (A1114, Cl, Cl, Me, 3-ethyloxybutyl, OCH2),(A1115, Cl, Cl, Me, 3-ethyloxypentyl, OCH2), (A1116, Cl, Cl, Me,3-ethyloxyhexyl, OCH2), (A1117, Cl, Cl, Me, 3-ethyloxy-4-methylpentyl,OCH2), (A1118, Cl, Cl, Me, 3-ethyloxyheptyl, OCH2), (A1119, Cl, Cl, Me,3-ethyloxy-5-methylhexyl, OCH2), (A1120, Cl, Cl, Me,3-ethoxy-4,4-dimethylpentyl, OCH2), (A1121, Cl, Cl, Me, 3-ethyloxyoctyl,OCH2), (A1122, Cl, Cl, Me, 3-ethyloxy-5,5-dimethylhexyl, OCH2), (A1124,Cl, Cl, Me, 3-n-propyloxybutyl, OCH2), (A1125, Cl, Cl, Me,3-n-propyloxypentyl, OCH2), (A1126, Cl, Cl, Me, 3-n-propyloxyhexyl,OCH2), (A1127, Cl, Cl, Me, 3-n-propyloxy-4-methylpentyl, OCH2), (A1128,Cl, Cl, Me, 3-n-propyloxyheptyl, OCH2), (A1129, Cl, Cl, Me,3-n-propyloxy-5-methylhexyl, OCH2), (A1130, Cl, Cl, Me,3-n-propyloxy-4,4-dimethylpentyl, OCH2), (A1131, Cl, Cl, Me,3-n-propyloxyoctyl, OCH2), (A1132, Cl, Cl, Me,3-n-propyloxy-5,5-dimethylhexyl, OCH2), (A1133, Cl, Cl, Me,3-isopropyloxypropyl, O(CH2), (A1134, Cl, Cl, Me, 3-isopropyloxybutyl,OCH2), (A1135, Cl, Cl, Me, 3-isopropyloxypentyl, OCH2), (A1136, Cl, Cl,Me, 3-isopropyloxyhexyl, OCH2), (A1137, Cl, Cl, Me,3-isopropyloxy-4-methylpentyl, OCH2), (A1138, Cl, Cl, Me,3-isopropyloxyheptyl, OCH2), (A1139, Cl, Cl, Me,3-isopropyloxy-5-methylhexyl, OCH2), (A1140, Cl, Cl, Me,3-isopropyloxy-4,4-dimethylpentyl, OCH2), (A1141, Cl, Cl, Me,3-isopropyloxyoctyl, OCH2), (A1142, Cl, Cl, Me,3-isopropyloxy-5,5-dimethylhexyl, OCH2), (A1143, Cl, Cl, Me,3-n-butyloxypropyl, OCH2), (A1144, Cl, Cl, Me, 3-n-butyloxybutyl, OCH2),(A1145, Cl, Cl, Me, 3-n-butyloxypentyl, OCH2), (A1146, Cl, Cl, Me,3-n-butyloxyhexyl, OCH2), (A1147, Cl, Cl, Me,3-n-butyloxy-4-methylpentyl, OCH2), (A1148, Cl, Cl, Me,3-n-butyloxyheptyl, OCH2), (A1149, Cl, Cl, Me,3-n-butyloxy-5-methylhexyl, OCH2), (A1150, Cl, Cl, Me,3-n-butyloxy-4,4-dimethylpentyl, OCH2), (A1151, Cl, Cl, Me,3-n-butyloxyoctyl, OCH2), (A1152, Cl, Cl, Me,3-n-butyloxy-5,5-dimethylhexyl, OCH2), (A1153, Cl, Cl, Me,3-isobutyloxypropyl, OCH2), (A1154, Cl, Cl, Me, 3-isobutyloxybutyl,OCH2), (A1155, Cl, Cl, Me, 3-isobutyloxypentyl, OCH2), (A1156, Cl, Cl,Me, 3-isobutyloxyhexyl, OCH2), (A1157, Cl, Cl, Me,3-isobutyloxy-4-methylpentyl, OCH2), (A1158, Cl, Cl, Me,3-isobutyloxyheptyl, OCH2), (A1159, Cl, Cl, Me,3-isobutyloxy-5-methylhexyl, OCH2), (A1160, Cl, Cl, Me,3-isobutyloxy-4,4-dimethylpentyl, OCH2), (A1161, Cl, Cl, Me,3-isobutyloxyoctyl, OCH2), (A1162, Cl, Cl, Me,3-isobutyloxy-5,5-dimethylhexyl, OCH2), (A1163, Cl, Cl, Me,3-t-butyloxypropyl, OCH2), (A1164, Cl, Cl, Me, 3-t-butyloxybutyl, OCH2),(A1165, Cl, Cl, Me, 3-t-butyloxypentyl, OCH2), (A1166, Cl, Cl, Me,3-t-butyloxyhexyl, OCH2), (A1167, Cl, Cl, Me,3-t-butyloxy-4-methylpentyl, OCH2), (A1168, Cl, Cl, Me,3-t-butyloxyheptyl, OCH2), (A1169, Cl, Cl, Me,3-t-butyloxy-5-methylhexyl, OCH2), (A1170, Cl, Cl, Me,3-t-butyloxy-4,4-dimethylpentyl, OCH2), (A1171, Cl, Cl, Me,3-t-butyloxyoctyl, OCH2), (A1172, Cl, Cl, Me,3-t-butyloxy-5,5-dimethylhexyl, OCH2), (A1173, Cl, Cl, Me,3-n-pentyloxypropyl, OCH2), (A1174, Cl, Cl, Me, 3-n-pentyloxybutyl,OCH2), (A1175, Cl, Cl, Me, 3-n-pentyloxypentyl, OCH2), (A1176, Cl, Cl,Me, 3-n-pentyloxyhexyl, OCH2), (A1177, Cl, Cl, Me,3-n-pentyloxy-4-methylpentyl, OCH2), (A1178, Cl, Cl, Me,3-n-pentyloxyheptyl, OCH2), (A1179, Cl, Cl, Me,3-n-pentyloxy-5-methylhexyl, OCH2), (A1180, Cl, Cl, Me,3-n-pentyloxy-4,4-dimethylpentyl, OCH2), (A1181, Cl, Cl, Me,3-n-pentyloxyoctyl, OCH2), (A1182, Cl, Cl, Me,3-n-pentyloxy-5,5-dimethylhexyl, OCH2), (A1183, Cl, Cl, Me,3-neopentyloxypropyl, OCH2), (A1184, Cl, Cl, Me, 3-neopentyloxybutyl,OCH2), (A1185, Cl, Cl, Me, 3-neopentyloxypentyl, OCH2), (A1186, Cl, Cl,Me, 3-neopentyloxyhexyl, OCH2), (A1187, Cl, Cl, Me,3-neopentyloxy-4-methylpentyl, OCH2), (A1188, Cl, Cl, Me,3-neopentyloxyheptyl, OCH2), (A1189, Cl, Cl, Me,3-neopentyloxy-5-methylhexyl, OCH2), (A1190, Cl, Cl, Me,3-neopentyloxy-4,4-dimethylpentyl, OCH2), (A1191, Cl, Cl, Me,3-neopentyloxyoctyl, OCH2), (A1192, Cl, Cl, Me,3-neopentyloxy-5,5-dimethylhexyl, OCH2), (A1193, Cl, Cl, OMe,3-methyloxypropyl, OCH2), (A1194, Cl, Cl, OMe, 3-methyloxybutyl, OCH2),(A1195, Cl, Cl, OMe, 3-methyloxypentyl, OCH2), (A1196, Cl, Cl, OMe,3-methyloxyhexyl, OCH2), (A1197, Cl, Cl, OMe,3-methyloxy-4-methylpentyl, OCH2), (A1198, Cl, Cl, OMe,3-methyloxyheptyl, OCH2), (A1199, Cl, Cl, OMe,3-methyloxy-5-methylhexyl, OCH2), (A1200, Cl, Cl, OMe,3-methoxy-4,4-dimethylpentyl, OCH2), (A1201, Cl, Cl, OMe,3-methyloxyoctyl, OCH2), (A1202, Cl, Cl, OMe,3-methyloxy-5,5-dimethylhexyl, OCH2), (A1203, Cl, Cl, OMe,3-ethyloxypropyl, OCH2), (A1204, Cl, Cl, OMe, 3-ethyloxybutyl, OCH2),(A1205, Cl, Cl, OMe, 3-ethyloxypentyl, OCH2), (A1206, Cl, Cl, OMe,3-ethyloxyhexyl, OCH2), (A1207, Cl, Cl, OMe, 3-ethyloxy-4-methylpentyl,OCH2), (A1208, Cl, Cl, OMe, 3-ethyloxyheptyl, OCH2), (A1209, Cl, Cl,OMe, 3-ethyloxy-5-methylhexyl, OCH2), (A1210, Cl, Cl, OMe,3-etoxy-4,4-dimethylpentyl, OCH2), (A1211, Cl, Cl, OMe, 3-ethyloxyoctyl,OCH2), (A1212, Cl, Cl, OMe, 3-ethyloxy-5,5-dimethylhexyl, OCH2), (A1213,Cl, Cl, OMe, 3-n-propyloxypropyl, OCH2), (A1214, Cl, Cl, OMe,3-n-propyloxybutyl, OCH2), (A1215, Cl, Cl, OMe, 3-n-propyloxypentyl,OCH2), (A1216, Cl, Cl, OMe, 3-n-propyloxyhexyl, OCH2), (A1217, Cl, Cl,OMe, 3-n-propyloxy-4-methylpentyl, OCH2), (A1218, Cl, Cl, OMe,3-n-propyloxyheptyl, OCH2), (A1219, CL, Cl, OMe,3-n-propyloxy-5-methylhexyl, OCH2), (A1220, Cl, Cl, OMe,3-n-propyloxy-4,4-dimethylpentyl, OCH2), (A1221, Cl, Cl, OMe,3-n-propyloxyoctyl, OCH2), (A1222, Cl, Cl, OMe,3-n-propyloxy-5,5-dimethylhexyl, OCH2), (A1223, Cl, Cl, OMe,3-isopropyloxypropyl, OCH2), (A1224, Cl, Cl, OMe, 3-isopropyloxybutyl,OCH2), (A1225, Cl, Cl, OMe, 3-isopropyloxypentyl, OCH2), (A1226, Cl, Cl,OMe, 3-isopropyloxyhexyl, OCH2), (A1227, Cl, Cl, OMe,3-isopropyloxy-4-methylpentyl, OCH2), (A1228, Cl, Cl, OMe,3-isopropyloxyheptyl, OCH2), (A1229, Cl, Cl, OMe,3-isopropyloxy-5-methylhexyl, OCH2), (A1230, Cl, Cl, OMe,3-isopropyloxy-4,4-dimethylpentyl, OCH2), (A1231, Cl, Cl, OMe,3-isopropyloxyoctyl, OCH2), (A1232, Cl, Cl, OMe,3-isopropyloxy-5,5-dimethylhexyl, OCH2), (A1233, Cl, Cl, OMe,3-n-butyloxypropyl, OCH2), (A1234, Cl, Cl, OMe, 3-n-butyloxybutyl,OCH2), (A1235, Cl, Cl, OMe, 3-n-butyloxypentyl, OCH2), (A1236, Cl, Cl,OMe, 3-n-butyloxyhexyl, OCH2), (A1237, Cl, Cl, OMe,3-n-butyloxy-4-methylpentyl, OCH2), (A1238, Cl, Cl, OMe,3-n-butyloxyheptyl, OCH2), (A1239, Cl, Cl, OMe,3-n-butyloxy-5-methylhexyl, OCH2), (A1240, Cl, Cl, OMe,3-n-butyloxy-4,4-dimethylpentyl, OCH2), (A1241, Cl, Cl, OMe,3-n-butyloxyoctyl, OCH2), (A1242, Cl, Cl, OMe,3-n-butyloxy-5,5-dimethylhexyl, OCH2), (A1243, Cl, Cl, OMe,3-isobutyloxypropyl, OCH2), (A1244, Cl, Cl, OMe, 3-isobutyloxybutyl,OCH2), (A1245, Cl, Cl, OMe, 3-isobutyloxypentyl, OCH2), (A1246, Cl, Cl,OMe, 3-isobutyloxyhexyl, OCH2), (A1247, Cl, Cl, OMe,3-isobutyloxy-4-methylpentyl, OCH2), (A1248, Cl, Cl, OMe,3-isobutyloxyheptyl, OCH2), (A1249, Cl, Cl, OMe,3-isobutyloxy-5-methylhexyl, OCH2), (A1250, Cl, Cl, OMe,3-isobutyloxy-4,4-dimethylpentyl, OCH2), (Ak251, Cl, Cl, OMe,3-isobutyloxyoctyl, OCH2), (A1252, Cl, Cl, OMe,3-isobutyloxy-5,5-dimethylhexyl, OCH2), (A1253, Cl, Cl, OMe,3-t-butyloxypropyl, OCH2), (A1254, Cl, Cl, OMe, 3-t-butyloxybutyl,OCH2), (A1255, Cl, Cl, OMe, 3-t-butyloxypentyl, OCH2), (A1256, Cl, Cl,OMe, 3-t-butyloxyhexyl, OCH2), (A1257, Cl, Cl, OMe,3-t-butyloxy-4-methylpentyl, OCH2), (A1258, Cl, Cl, OMe,3-t-butyloxyheptyl, OCH2), (A1259, Cl, Cl, OMe,3-t-butyloxy-5-methylhexyl, OCH2), (A1260, Cl, Cl, OMe,3-t-butyloxy-4,4-dimethylpentyl, OCH2), (A1261, Cl, Cl, OMe,3-t-butyloxyoctyl, OCH2), (A1262, Cl, Cl, OMe,3-t-butyloxy-5,5-dimethylhexyl, OCH2), (A1263, Cl, Cl, OMe,3-n-pentyloxypropyl, OCH2), (A1264, Cl, Cl, OMe, 3-n-pentyloxybutyl,OCH2), (A1265, Cl, Cl, OMe, 3-n-pentyloxypentyl, OCH2), (A1266, Cl, Cl,OMe, 3-n-pentyloxyhexyl, OCH2), (A1267, Cl, Cl, OMe,3-n-pentyloxy-4-methylpentyl, OCH2), (A1268, Cl, Cl, OMe,3-n-pentyloxyheptyl, OCH2), (A1269, Cl, Cl, OMe,3-n-pentyloxy-5-methylhexyl, OCH2), (A1270, Cl, Cl, OMe,3-n-pentyloxy-4,4-dimethylpentyl, OCH2), (A1271, Cl, Cl, OMe,3-n-pentyloxyoctyl, OCH2), (A1272, Cl, Cl, OMe,3-n-pentyloxy-5,5-dimethylhexyl, OCH2), (A1273, Cl, Cl, OMe,3-neopentyloxypropyl, OCH2), (A1274, Cl, Cl, OMe, 3-neopentyloxybutyl,OCH2), (A1275, Cl, Cl, OMe, 3-neopentyloxypentyl, OCH2), (A1276, Cl, Cl,OMe, 3-neopentyloxyhexyl, OCH2), (A1277, Cl, Cl, OMe,3-neopentyloxy-4-methylpentyl, OCH2), (A1278, Cl, Cl, OMe,3-neopentyloxyheptyl, OCH2), (A1279, Cl, Cl, OMe,3-neopentyloxy-5-methylhexyl, OCH2), (A1280, Cl, Cl, OMe,3-neopentyloxy-4,4-dimethylpentyl, OCH2), (A1281, Cl, Cl, OMe,3-neopentyloxyoctyl, OCH2), (A1282, Cl, Cl, OMe,3-neopentyloxy-5,5-dimethylhexyl, OCH2), (A1283, F, F, F,3-neopentyloxypropyl, CH2CH2), (A1284, F, F, Cl, 3-neopentyloxypropyl,CH2CH2), (A1285, Cl, Cl, F, 3-methyloxyhexyl, CH2CH2), (A1286, Cl, Cl,Cl, 3-methyloxyhexyl, CH2CH2), (A1287, Cl, Cl, F, 3-ethyloxypropyl,CH2CH2), (A1288, Cl, Cl, Cl, 3-ethyloxypropyl, CH2CH2), (A1289, Cl, Cl,F, 3-n-butyloxypropyl, CH2CH2), (A1290, Cl, Cl, Cl, 3-n-butyloxypropyl,CH2CH2), (A1291, Me, Me, Me, 3-methyloxyhexyl, CH2CH2), (A1292, Me, Me,Me, 3-ethyloxypropyl, CH2CH2), (A1293, Me, Me, Me, 3-n-butyloxypropyl,CH2CH2), (A1294, Me, Me, Me, 3-neopentyloxypropyl, CH2CH2)

Example 79 Synthesis of Compound (B1)

1) Synthesis of2-[2-fluoro-3-(1-hydroxyhexyl)phenyl]-2-methyl-1,3-dioxolane (16)

To a THF (48 mL) solution of 2-(2-fluorophenyl)-2-methyl-1,3-dioxolane(6.0 g) and N,N,N′,N″,N″-pentamethyldiethylenetriamine (8.0 mL) wasadded 1.58 M hexane solution of n-butyl lithium (25.3 mL) dropwise at−78° C. After the reaction mixture was stirred for 1 h, n-hexylaldehyde(5.88 mL) was added into the reaction mixture. After the reactionmixture was stirred for additional 1 h at −78° C., a saturated ammoniumchloride aqueous solution was added into the reaction mixture. Thereaction mixture was extracted with ethyl acetate, and the organic layerwas washed with water, and brine, dried over magnesium sulfate, andevaporated. The obtained residue was purified by column chromatography(hexane:ethyl acetate=4:1) to obtain the compound (16) 6.9 g.

¹H-NMR(CDCl₃) 7.39-7.46 (m, 2H), 7.11 (t, 1H, J=7.6 Hz), 5.02-5.07 (m,1H), 4.02-4.11 (m, 2H), 3.82-3.91 (m, 2H), 1.73-1.81 (m, 5H), 1.24-1.70(m, 6H), 0.86-0.89 (m, 3H).

2) Synthesis of2-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-2-methyl-1,3-dioxolane (17)

To a DMF (35 mL) solution of2-[2-fluoro-3-(1-hydroxyhexyl)phenyl]-2-methyl-1,3-dioxolane e (6.9 g)and methyl iodide (6-1 mL) was added sodium hydride (1.96 g) underice-cooling. After the reaction mixture was stirred at room temperaturefor 1 h, a saturated ammonium chloride aqueous solution was added intothe reaction mixture. The reaction mixture was extracted with ethylacetate, and the organic layer was washed with water, and brine, driedover magnesium sulfate, and evaporated. The obtained residue waspurified by column chromatography (hexane:ethyl acetate=20:1) to obtainthe compound (17) 6.99 g.

¹H-NMR(CDCl₃) 7.33-7.44 (m, 2H), 7.12 (t, 1H, J=7.6 Hz), 4.56 (dd, 1H,J=7.6 Hz, 2.1 Hz), 4.02-4.14 (m, 2H), 3.85-3.92 (m, 2H), 3.25 (s, 3H),158-1.77 (m, 5H), 1.21-1.46 (m, 6H), 0.86 (t, 3H, J=6.7 Hz).

3) Synthesis of 2-fluoro-3-(1-methyloxyhexyl)acetophenone (18)

To a methanol (10 mL) solution of2-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-2-methyl-1,3-dioxolane (6.98 g)was added 35% hydrochloric acid (0.5 mL) at room temperature. Asaturated sodium hydrogencarbonate aqueous solution was added into thereaction mixture. The reaction mixture was extracted with ethyl acetate,and the organic layer was dried over magnesium sulfate, and evaporatedto obtain the compound (18).

1H-NMR(CDCl3) 7.40-7.80 (m, 1H), 7.56-7.62 (m, 1H), 7.21-7.26 (t, 1H,J=7.6 Hz), 4.54-4.58 (m, 1H), 3.26 (s, 3-H), 2.66 (d, 3H, J=4.9 Hz),1.62-1.77 (m, 2H), 1.29-1.44 (m, 6H), 0.85-0.90 (m, 3H).

4) Synthesis of 4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylamine(19)

To a 10% methanol-chloroform (60 mL) solution of2-fluoro-3-(1-methyloxyhexyl)acetophenone was added bromine (1.21 mL),and the reaction mixture was stirred for 1 h. After the solvent wasevaporated, the residue was dissolved in ethanol (60 mL), and thiourea(1.8 g) was added into the reaction mixture. The reaction mixture washeated at reflux for 7 h, and evaporated. A saturated sodiumhydrogencarbonate aqueous solution was added into the residue, and themixture was extracted with ethyl acetate, dried over magnesium sulfate,and evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=4:1) to obtain the compound (19)5.0 g.

¹H-NMR(CDCl3) 7.92 (dt, 1H, J=7.6 Hz, 1.8 Hz), 7.28-7.34 (m, 1H), 7.20(t, 1H, J=7.6 Hz), 7.02 (d, 1H, J=2.4 Hz), 4.56-4.60 (m, 1H), 3.25 (s,3H), 1.63-1.83 (m, 2H), 1.24-1.47 (m, 6H), 0.81-0.89 (m, 3H).

5) Synthesis of ethyl3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylate(20)

To a DMF (6 mL) solution of4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylamine (318 mg),3-(4-bromo-2,6-difluorophenyl)-2-methylacrylic acid ethyl ester (300mg), and dichlorobistriphenylphosphinepalladium (36 mg) was addedtriethylamine (0.43 mL). The reaction mixture was stirred under carbonmonoxide atmosphere at 85° C. for 16 h. Water was poured into thereaction mixture, and the reaction mixture extracted with ethyl acetate,and the organic layer was washed with water, and brine, dried overmagnesium sulfate, and evaporated. The obtained residue was purified bycolumn chromatography (hexane:ethyl acetate=4:1) to obtain the compound(20) 500 mg.

6) Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1)

To a mixture of THF (2 mL), methanol (2 mL), and 2N sodium hydroxideaqueous solution of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl{phenyl}-2-methylacrylicacid ethyl ester (500 mg) was stirred at room temperature for 3 h. Thereaction mixture was acidified with hydrochloric acid, and extractedwith ethyl acetate. The organic layer was washed with water, and brine,dried over magnesium sulfate, and evaporated. The residue wasrecrystallized from ethyl acetate to obtain the compound (B1) 370 mg.

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.94-8.08 (m, 3H), 7.66 (d, 1H, J=2.1Hz), 7.30-7.42 (m, 3H), 4.57 (t, 1H, J=6.4 Hz), 3.18 (s, 3H), 1.81 (s,3H), 1.60-1.81 (m, 2H), 1.20-1.50 (m, 6H), 0.80-0.90 (m, 3H).

Example 80 Synthesis of compound (B533)

1) Synthesis of (methyloxymethyloxycarbonylmethyl)triphenylphosphoniumchloride (22)

Methyl dimethyloxyacetate (15 g) was dissolved in acetyl chloride (9.7g), and iodine (0.09 g) was added into the mixture. The reaction mixturewas stirred for 3 h, and evaporated. The residue was dissolved again indichloromethane (200 mL), and triphenylphosphine (29.5 g) was added intothe reaction mixture. The reaction mixture was stirred for 3 h, andevaporated to obtain the compound (22) 44 g.

¹H-NMR(CDCl₃) 7.96-8.03 (m, 6H), 7.63-7.78 (m, 9H), 3.90 (s, 3H), 3.60(s, 3H), 3.43 (s, 1H).

2) Synthesis of methyl(Z)-3-(4-bromo-2,6-difluorophenyl)-2-methyloxyacrylate (23)

4-Bromo-2,6-difluorobenzaldehyde (31.2 g) was dissolved indichloromethane (300 mL), and(methyloxymethyloxycarbonylmethyl)triphenylphosphonium chloride (113.3g) was added into the mixture. To the reaction mixture was addedtriethylamine (59 mL) dropwise, and the reaction mixture was stirred for3 h. To the reaction mixture were added ice-water and 2N hydrochloricacid, and the reaction mixture was extracted with ethyl acetate. Theorganic layer was washed with water, and brine, dried over magnesiumsulfate, evaporated. The obtained residue was purified by columnchromatography (hexane:ethyl acetate=10:1) to obtain the compound (23)32.1 g.

¹H-NMR(CDCl₃) 7.08-7.14 (m, 2H), 6.67-6.68 (m, 1H), 3.87 (s, 3H), 3.76(s, 3H).

3) Synthesis of methyl(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylate(241)

4-[2-Fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylamine (460 mg) andmethyl (Z)-3-(4-bromo-2,6-difluorophenyl)-2-methyloxyacrylate (462 mg),and dichlorobistriphenylphosphinepalladium (150 mg) were dissolved inDMF (6 mL). Triethylamine (0.84 mL) was added into the mixture, and thereaction mixture was stirred under carbon monoxide atmosphere at 85° C.for 16 h. Water added into the reaction mixture, and the reactionmixture was extracted with ethyl acetate. The organic layer was washedwith water, and brine, dried over magnesium sulfate, evaporated. Theobtained residue was purified by column chromatography (hexane ethylacetate=4:1) to obtain the compound (24) 630 mg.

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.01-8.05 (m, 1H), 7.89-7.95 (m, 2H),7.65 (d, 1H, J=2.4 Hz), 7.31-7.39 (m, 2H), 6.66 (s, 1H), 4.55-4.60 (m,1H), 3.80 (s, 3H), 3.72 (s, 3H), 3.18 (s, 3H), 1.64-1.76 (m, 2H),1.26-1.41 (m, 6H), 0.81-0.86 (m, 3H).

4) Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B533)

Methyl(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylate(630 mg) was dissolved in a mixture of THF (2 mL), methanol (2 mL), and2N sodium hydroxide aqueous solution (2 mL), and the mixture was stirredat room temperature for 3 h. The reaction mixture was acidified withhydrochloric acid, and the reaction mixture was extracted with ethylacetate. The organic layer was washed with water, and brine, dried overmagnesium sulfate, evaporated. The obtained residue was recrystallizedfrom ethyl acetate to obtain the compound (B533) 590 mg.

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.00-8.05 (m, 1H), 7.89-7.95 (m, 2H),7.65 (d, 1H, J=2.4 Hz), 7.31-7.39 (m, 2H), 6.67 (s, 1H), 4.55-4.59 (m,1H), 3.72 (s, 3H), 3.18 (s, 3H), 1.64-1.76 (m, 2H), 1.26-1.41 (m, 6H),0.81-0.86 (m, 3H).

B2 to B101, B121, B122, B134, B169, B170, B195, B216, B233, B255, B264,B347 to B349, B354, B355, B380, B397, B418, B419, B425, B488, B505,B519, B521, B790, B896, B897, B899, B905, B927, B936, B958, B967, B1053,B1054, B1059, B1060, B1102, B1122, B1124, B1238, B1250, B1429, B1432,B1438, B1728 to B1739, B1742, B1744, B1746 to B1757, B1762 to B2047,B2049, B2051 to B2090, and B2097 to B2100 were synthesized by similarmethod mentioned above.

Example 81 Synthesis of3-(2,6-difluoro-4-{4-[3-(3,3-dimethylbutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.88-8.02 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.28 (dt, 1H, J=7.0 Hz, 1.5 Hz), 7.22 (t, 1H, J=7.6Hz), 2.60-2.70 (m, 2H), 1.81 (d, 3H, J=1.5 Hz), 1.42-1.55 (m, 2H), 0.97(s, 9H).

Example 82 Synthesis of3-(4-{4-[3-(1-cyclohexyl-1-methyloxymethyl)-2-fluoropenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B3)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.93-8.08 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.28-7.48 (m, 3H), 4.32 (d, 1H, J=7.0 Hz), 3.15 (s, 3H), 1.90 (m,1H), 1.81 (d, 3H, J=1.5 Hz), 0.90-1.80 (m, 10H).

Example 83 Synthesis of3-{2,6-difluoro-4-[4-(2-fluoro-3-pentylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B4)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.90-8.02 (m, 3H), 7.64 (d, 1H J=2.1Hz), 7.34 (s, 1H), 7.18-7.32 (m, 2H), 2.68 (t, 2H, J=7.6 Hz), 1.81 (s,3H), 1.61 (t, 2H, J=6.9 Hz), 1.20-1.40 (m, 4H), 0.88 (t, 3H, J=6.0 Hz).

Example 84 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B5)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.90-8.02 (m, 3H), 7.64 (s, 1H), 7.34(s, 1H), 7.18-7.33 (m, 2H), 2.67 (t, 2H, J=7.2 Hz), 1.81 (s, 3H),1.50-1.70 (m, 3H), 1.19-1.36 (m, 2H), 0.86 (d, 6H, J=6.7 Hz).

Example 85 Synthesis of3-(4-{4-[3-(1-cyclohexyl-1-ethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B6)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.00-8.06 (m, 2H), 7.97 (d, 1H, J=8.5Hz), 7.64 (d, 1H, J=−2.7 Hz), 7.30-7.38 (m, 3H), 4.41 (d, 1H, J=7.3 Hz),3.23-3.40 (m, 2H), 1.94 (m, 1H), 1.81 (d, 3H, J=1.5 Hz), 0.90-1.75 (m,10H), 1.10 (t, 3H, J=7.0 Hz).

Example 86 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(2,4-dimethyl-3-methyloxy-3-pentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B7)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.91-8.08 (m, 3H), 7.57 (d, 1H, J=3.1Hz), 7.30-7.42 (m, 3H), 3.32 (s, 3H), 2.50-2.70 (m, 2H), 1.81 (s, 3H),0.90 (d, 12H, J=6.7 Hz).

Example 87 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methyloxy-4-pentyl)phenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B8)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.04 (m, 3H), 7.62 (d, 1H, J=2.7Hz), 7.51 (dt, 1H, J=1.8, 7.8 Hz), 7.35 (s, 1H), 7.27 (t, 1H, J=7.8 Hz),3.17 (s, 3H), 1.82-2.02 (m, 4H), 1.81 (d, 3H, J=1.5 Hz), 0.75-1.35 (m,10H).

Example 88 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B9)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.92-8.08 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.30-7.41 (m, 3H), 4.57 (t, 1H, J=6.4 Hz), 3.18 (s, 3H), 1.81 (d,3H, J=1.8 Hz), 1.60-1.80 (m, 2H), 1.15-1.40 (m, 14H), 0.84 (t, 3H, J=6.5Hz).

Example 89 Synthesis of3-(2,6-difluoro-4-{4-[3-(1-ethyloxy-2,2-dimethylpropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B10)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.93-8.08 (m, 3H), 7.62 (d, 1H, J=2.7Hz), 7.30-7.40 (m, 3H), 4.42 (s, 1H), 3.20-3.40 (m, 2H), 1.81 (d, 3H,J=1.5 Hz), 1.11 (t, 311, J=7.0 Hz), 0.91 (s, 9H).

Example 90 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B11)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 7.93-8.08 (m, 3H), 7-66 (d, 1H, J=2.7Hz), 7.30-7.43 (m, 3H), 4.55 (t, 1H, J=6.6 Hz), 3.18 (s, 3H), 1.81 (s,3H), 1.10-1.85 (m, 5H), 0.84 (d, 6H, J=6.7 Hz).

Example 91 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B12)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-7.98 (m, 3H), 7.64 (d, 1H, J=2.3Hz), 7.20-7.34 (m, 3H), 3.20 (s, 3H), 3.10 (qint, 1H, J=5.6 Hz), 2.69(t, 2H, J=7.7 Hz), 3.18 (s, 3H), 1.81 (d, 3H, J=1.6 Hz), 1.57-1.67 (m,2H), 1.39-1.50 (m, 4H), 0.81 (t, 3H, J=7.5 Hz).

Example 92 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B13)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.06 (m, 3H), 7.63 (d, 1H, J=2.7Hz), 7.28-8.38 (m, 3H), 4.32 (s, 1H), 3.14 (s, 3H), 1.81 (d, 3H, J=1.6Hz), 0.91 (2, 9H).

Example 93 Synthesis of3-(4-{4-[3-(1-cyclohexyl-1-n-pentyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B14)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.99 (m, 1H), 7.98 (s, 1H), 7.95 (s,1H), 7.64 (d, 1H, J=2.4 Hz), 7.28-7.36 (m, 3H), 4.39 (d, 1H, J=6.9 Hz),3.24 (t, 2H, J=5.7 Hz), 1.93 (m, 1H), 1.81 (d, 3H, J=1.8 Hz), 0.94-1.76(m, 16H), 0.84 (t, 3H, J=7.2 Hz).

Example 94 Synthesis of3-(2,6-difluoro-4-{4-[3-(2,2-dimethyl-1-n-pentyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B15)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.96-8.05 (m, 3H), 7.62 (s, 1H),7.26-7.37 (m, 3H), 4.39 (s, 1H), 3.22 (t, 2H, J=6.6 Hz), 1.81 (s, 3H),1.44-1.57 (m, 211), 1.19-1.38 (m, 4H), 0.91 (2, 9H), 0.84-0.88 (m, 3H).

Example 95 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methylthio-1-n-pentyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B16)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.05 (m, 3H), 7.66 (d, 1H, J=2.4Hz), 7.32-7.42 (m, 3H), 4.82 (m, 1H), 3.28-3.50 (m, 2H), 2.58 (t, 2H,J=7.8 Hz), 2.06 (s, 3H), 1.87-2.02 (m, 2H), 1.81 (d, 3H, J=1.5 Hz),1.44-1.58 (m, 2H), 1.20-1.35 (m, 4H), 0.85 (t, 3H, J=6.9 Hz).

Example 96 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methyloxy-3-methylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B17)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.90-8.00 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.12-7.34 (m, 3H), 3.14 (s, 3H), 2.64-2.70 (m, 2H), 1.81 (d, 3H,J=1.5 Hz), 1.69-1.75 (m, 21), 1.17 (s, 6H).

Example 97 Synthesis of3-[2,6-difluoro-4-(4-{2-fluoro-3-{1-(3-methylbutyloxypropyl}phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B18)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.95-8.04 (m, 3H), 7.64 (d, 1H, J=2.7Hz), 7.31-7.40 (m, 3H), 4.59 (t, 1H, J=6.6 Hz), 3.08-3.50 (m, 2H), 1.81(d, 3H, J=1.5 Hz), 1.65-1.76 (m, 3H), 1.41 (q, 2H, J=6.6 Hz), 0.81-0.91(m, 9H).

Example 98 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-pentyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B19)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.91-8.06 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.31-7.41 (m, 3H), 4.59 (t, 1H, J=6.6 Hz), 3.25-3.38 (m, 2H); 1.81(d, 3H, J=1.8 Hz), 1.64-1.77 (m, 2H), 1.46-1.57 (m, 2H), 1.20-1.35 (m,4H), 0.89 (t, 3H, J=7.2 Hz), 0.85 (t, 3H, J=7.2 Hz).

Example 99 Synthesis of3-[4-(4-{3-(2,2-dimethylpropyloxy)propyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B20)

1H-NMR(DMSO-d6) 13.00 (s, 2H), 7.92-8.02 (m, 3H), 7.63 (s, 1H), 7.34 (s,1H), 7.22-7.30 (m, 2H), 3.42 (t, 2H, J=6.0 Hz), 3.04 (s, 2H), 2.76 (t,2H, J=7.8 Hz), 1.81-1.89 (m, 5H), 0.89 (s, 9H).

Example 100 Synthesis of3-[4-(4-{3-[1-cyclohexyl-1-(4-ethyloxybutyloxy)methyl]-2-fluorophenyl]thiazol-2-ylcarbarmoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B21)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.95-8.04 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.33 (d, 3H, J=7.2 Hz), 4.39 (d, 1H, J=6.9 Hz), 3.25-3.39 (m, 6H),1.95 (m, 1H), 1.81 (d, 3H, J=1.8 Hz), 1.45-1.76 (m, 9H), 1.36 (m, 1H),0.98-1.23 (m, 4H), 1.07 (t, 3H, J=6.6 Hz).

Example 101 Synthesis of3-[2,6-difluoro-4-(4-{3-[1-(4-ethyloxybutyloxy)propyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B22)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.04 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.31-7.40 (m, 3H), 4.60 (t, 1H, J=5.7 Hz), 3.33-3.37 (m, 6H), 1.81(d, 3H, J=1.5 Hz), 1.64-1.77 (m, 2H), 1.54 (s, 4H), 1.07 (t, 3H, J=6.9Hz), 0.89 (t, 3H, J=7.2 Hz).

Example 102 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyheptyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B23)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 7.95-8.05 (m, 3H), 7.64 (d, 1H,J=2.4Hz), 7.23-7.33 (m, 3H), 4.54 (t, 1H, J=6.5 Hz), 3.18 (s, 3H,), 1.81(d, 3H, J=1.3 Hz), 1.60-1.80 (m, 4H), 1.20-1.30 (m, 6H), 0.81-0.85 (m,3H).

Example 103 Synthesis of3-(2,6-difluoro-4-{4-[3-(1-ethyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B24)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.04 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.31-7.42 (m, 3H), 4.67-4.71 (m, 1H), 3.36 (t, 2H, J=7.0 Hz), 1.81(d, 3H, J=1.5 Hz), 1.60-1.78 (m, 2H), 1.27-1.44 (m, 2H), 1.12 (t, 3H,J=7.0 Hz), 0.89 (t, 3H, J=7.3 Hz).

Example 104 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyoctyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B25)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.05 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.31-8.38 (m, 3H), 4.56 (t, 1H, J=6.5 Hz), 3.18 (s, 3H), 1.81 (d,3H, J=1.4 Hz), 1.60-1.81 (m, 2H), 1.20-1.37 (m, 10H), 0.81-0.86 (m, 3H).

Example 105 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-pentyloxypentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B26)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.04 (m, 3H), 7.65 (d, 1H, J=2.0Hz), 7.30-7.40 (m, 3H), 4.62-4.66 (m, 1H), 3.28 (t, 2H, J=6.4 Hz), 1.80(s, 3H), 1.60-1.75 (m, 2H), 1.45-1.54 (m, 2H), 1.22-1.33 (m, 8H),0.83-0.87 (m, 6H).

Example 106 Synthesis of3-(2,6-difluoro-4-{4-[3-(1-ethyloxypentyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B27)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.95-8.04 (m, 3H), 7.64-7.65 (m, 1H),7.30-7.41 (m, 3H), 4.67 (t, 1H, J=6.9 Hz), 3.35 (q, 211, J=6.9 Hz), 1.81(d, 3H, J=1.3 Hz), 1.60-1.81 (m, 2H), 1.23-1.41 (m, 4H), 1.12 (t, 3H,J=6.9 Hz), 0.83-0.87 (m, 3H).

Example 107 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxynonyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B28)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.95-8.05 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.31-7.39 (m, 3H), 4.56 (t, 1H, J=7.2 Hz), 3.18 (s, 3H), 1.81 (s,3H), 1.55-1.85 (m, 2H), 1.17-1.45 (m, 12H), 0.83 (t, 3H, J=6.3 Hz).

Example 108 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B29)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 7.90-7.98 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.23-7.33 (m, 3H), 3.33 (s, 3H,), 3.20-3.28 (m, 1H,), 2.65-2.70 (m,2H,), 1.81 (d, 3H, J=1.4 Hz), 1.70-1.80 (m, 2H), 1.32-1.40 (m, 2H),1.20-1.30 (m, 6H), 0.81-0.85 (m, 3H).

Example 109 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-octyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B30)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.03 (m, 5H), 7.64 (d, 1H, J=2.3Hz), 7.30-7.42 (m, 5H), 4.81 (q, 1H, J=6.4 Hz), 3.23-3.40 (m, 2H), 1.81(s, 3H), 1.48-1.52 (m, 2H), 1.40 (d, 3H, J=6.4 Hz), 1.22-1.29 (m, 10H),0.82-0.86 (m, 3H).

Example 110 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-pentyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B31)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.04 (m, 3H), 7.65 (d, 1H, J=2.3Hz), 7.30-8.43 (m, 3H), 4.80 (q, 1H, J=6.3 Hz), 3.23-3.34 (m, 2H),1.48-1.55 (m, 2H), 1.41 (d, 3H, J=6.4 Hz), 1.22-1.30 (m, 4H), 0.83-0.88(m, 3H).

Example 111 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(n-decyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B32)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.04 (dt, 1H, J=7.7 Hz, 1.8 Hz),7.94-7.99 (m, 2H), 7.65 (d, 1H, J=2.5 Hz), 7.42 (t, 1H, J=7.0 Hz),7.28-7.33 (m, 2H), 4.57 (s, 2H), 3.48 (t, 2H, 6.6 Hz), 1.81 (d, 3H,J=1.3 Hz), 1.51-1.58 (m, 2H), 1.22-1.35 (m, 14H), 0.81-0.86 (m, 3H).

Example 112 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(n-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B33)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.04 (dt, 1H, J=7.5 Hz, 1.9 Hz),7.39-7.99 (m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.40-7.44 (m, 1H), 7.28-7.34(m, 2H), 4.58 (s, 2H), 3.49 (t, 2H, 6.4 Hz), 1.81 (d, 3H, J=1.4 Hz),1.51-1.60 (m, 2H), 1.28-1.32 (m, 4H), 0.84-0.89 (m, 3H).

Example 113 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-propyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B34)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 7.95-8.05 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.30-7.38 (m, 3H), 4.67 (t, 1H, J=6.4 Hz), 3.22 (t, 2H, J=6.5),1.81 (d, 3H, J=1.3 Hz), 1.30-1.84 (m, 6H), 0.81-0.85 (m, 6H).

Example 114 Synthesis of3-(4-{4-[3-(1-n-butyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B35)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 7.95-8.04 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.30-7.38 (m, 3H), 4.67 (t, 1H, J=6.4 Hz), 3.22 (t, 2H, J=6.5),1.81 (d, 3H, J=1.4 Hz), 1.30-1.84 (m, 8H), 0.81-0.85 (m, 6H).

Example 115 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-pentyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B36)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 7.94-8.04 (m, 3H), 7.64 (d, 1H, J=2.3Hz), 7.30-7.38 (m, 3H), 4.66 (t, 1H, J=6.5 Hz), 3.22 (t, 2H, J=6.5),1.81 (d, 3H, J=1.4 Hz), 1.26-1.70 (m, 10H), 0.81-0.85 (m, 6H).

Example 116 Synthesis of3-(4-{4-[3-(1-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B37)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.03 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.31-7.40 (m, 3H), 4.59 (t, 1H, J=6.6 Hz), 3.25-3.33 (m, 2H), 1.81(d, 3H, J=1.5 Hz), 1.64-1.76 (m, 2H), 1.44-1.55 (m, 2H), 1.28-1.40 (m,2H), 0.89 (t, 3H, J=7.2 Hz), 0.86 (t, 3H, J=7.2 Hz).

Example 117 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-hexyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (38)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.95-8.03 (m, 3H), 7.65 (s, 1H),7.30-7.39 (m, 3H), 4.58 (t, 1H, J=6.0 Hz), 3.18-3.47 (m, 2H), 1.81 (d,3H, J=1.5 Hz), 1.64-1.79 (m, 2H), 1.44-1.56 (m, 2H), 1.16-1.37 (m, 6H),0.89 (t, 3H, J=7.5 Hz), 0.84 (t, 3H, J=6.6 Hz).

Example 118 Synthesis of3-[2,6-difluoro-4-(4-{2-fluoro-3-[3-(4-methylpentyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B39)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.91-7.95 (m, 3H), 7.63 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.20-3.44 (m, 4H), 2.73 (t, 2H,J=7.2 Hz), 1.76-1.90 (m, 2H), 1.80 (s, 3H), 1.44-1.56 (m, 4H), 1.14-1.25(m, 2H), 0.86 (d, 6H, J=6.6 Hz).

Example 119 Synthesis of3-[2,6-difluoro-4-(4-{3-[3-(3,3-dimethylbutyloxy)propyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B40)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.91-7.98 (m, 3H), 7.63 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.37-3.41 (m, 4H), 2.74 (t, 2H,J=7.2 Hz), 1.81 (d, 3H, J=1.8 Hz), 1.78-1.87 (m, 2H), 1.44 (t, 2H, J=7.5Hz), 0.90 (s, 9H).

Example 120 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-n-propyloxypentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B41)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.04 (m, 3H), 7.65 (d, 1H, J=2.0Hz), 7.31-7.41 (m, 3H), 4.63-4.67 (m, 1H), 3.25 (t, 2H, J=6.6 Hz),1.64-1.81 (m, 5H), 1.52 (q, 2H, J=6.9 Hz), 1.26-1.40 (m, 4H), 0.82-0.90(m, 6H).

Example 121 Synthesis of3-(4-{4-[3-(1-n-butyloxypentyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl]-2-methylacrylicacid (B42)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.03 (m, 3H), 7.65 (d, 1H, J=2.3Hz), 7.31-7.41 (m, 3H), 4.63-4.67 (m, 1H), 3.29 (t, 2H, J=6.4 Hz), 1.81(s, 3H), 1.60-1.78 (m, 2H), 1.44-1.53 (m, 2H), 1.28-1.40 (m, 6H), 0.86(t, 6H, J=7.2H).

Example 122 Synthesis of3-[2,6-difluoro-4-(4-{3-[3-(2-ethylbutyloxy)propyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B43)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.91-7.99 (m, 3H), 7.63 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.25-3.42 (m, 4H), 2.74 (t, 2H,J=7.8 Hz), 1.80-1.88 (m, 2H), 1.81 (d, 3H, J=2.1 Hz), 1.25-1.42 (m, 5H),0.85 (t, 6H, J=7.5 Hz).

Example 123 Synthesis of3-[4-(4-{3-[3-(2-cyclopentylethyloxy)propyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B44)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.91-7.98 (m, 3H), 7.63 (d, 1H, J=2.7Hz), 7.34 (s, 1H), 7.20-7.30 (m, 2H), 3.24-3.44 (m, 4H), 2.74 (t, 2H,J=7.2 Hz), 1.81 (d, 3H, J=1.8 Hz), 1.66-1.89 (m, 4H), 1.40-1.64 (m, 5H),1.00-1.14 (m, 4H).

Example 124 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-n-pentyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B45)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.91-7.98 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.24-3.41 (m, 4H), 2.74 (t, 2H,J=7.8 Hz), 1.77-1.90 (m, 2H), 1.81 (d, 3H, J=1.8 Hz), 1.44-1.55 (m, 2H),1.23-1.36 (m, 4H), 0.84-0.89 (m, 3H).

Example 125 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-n-hexyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B46)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.91-7.99 (m, 3H), 7.64 (d, 1H, J=2.7Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.20-3.42 (m, 4H), 2.74 (t, 2H,J=7.2 Hz), 1.77-1.87 (m, 2H), 1.81 (d, 3H, J=1.8 Hz), 1.45-1.51 (m, 2H),1.20-1.36 (m, 6H), 0.86 (t, 3H, J=6.9 Hz).

Example 126 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyundecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B47)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.05 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.31-7.39 (m, 3H), 4.54-4.58 (m, 1H), 3.18 (s, 3H), 1.81 (s, 3H),1.60-1.80 (m, 2H), 1.21-1.36 (m, 16H), 0.81-0.86 (m, 3H).

Example 127 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxydodecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B48)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.05 (m, 3H), 7.64 (d, 1H, J=2.5Hz), 7.30-7.38 (m, 3H), 4.54-4.58 (m, 1H), 3.17 (s, 3H), 1.81 (d, 3H,J=1.4 Hz), 1.61-1.81 (m, 2H), 1.21-1.36 (m, 18H), 0.81-0.85 (m, 3H).

Example 128 Synthesis of3-(4-{4-[3-(3-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B49)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.91-8.00 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.34 (s, 1H), 7.21-7.30 (m, 2H), 3.34-3.42 (m, 4H), 2.74 (t, 2H,J=7.2 Hz), 1.78-1.88 (m, 5H), 1.44-1.53 (m, 2H), 1.25-1.39 (m, 2H), 0.88(t, 3H, J=7.2 Hz).

Example 129 Synthesis of3-(4-{4-[3-(1-n-butyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B50)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.03 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.31-7.43 (m, 3H), 4.77-4.84 (m, 1H), 3.24-3.41 (m, 2H), 1.81 (s,3H), 1.45-1.55 (m, 2H), 1.41 (d, 3H, J=6.3 Hz), 1.29-1.37 (m, 2H),0.83-0.88 (m, 3H).

Example 130 Synthesis of3-(4-{4-[3-(1,4-dibutyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B51)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.00-8.04 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.31-7.41 (m, 3H), 4.68 (t, 1H, J=6.2 Hz), 3.28-3.33 (m, 6H), 1.81(d, 3H, J=1.8 Hz), 1.60-1.76 (m, 4H), 1.40-1.52 (m, 4H), 1.23-1.37 (m,4H), 0.86 (t, 3H, J=7.2 Hz).

Example 131 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-n-hexyloxy-1-methyloxyproyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B52)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.01-8.06 (m, 2H), 7.97 (d, 1H, J=8.7Hz), 7.65 (d, 1H, J=2.4 Hz), 7.31-7.40 (m, 3H), 4.71 (t, 1H, J=6.6 Hz),3.26-3.36 (m, 4H), 3.18 (s, 3H), 1.87-2.00 (m, 2H), 1.81 (s, 3H),1.39-1.54 (m, 2H), 1.20-1.32 (m, 6H), 0.85 (t, 3H, J=6.6 Hz).

Example 132 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-4-n-pentyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}-phenyl)-2-methylacrylicacid (B53)

1H-NMR(DMSO-d6) 13.02 &s, 2H), 8.00-8.06 (m, 2H), 7.97 (d, 1H, J=8.4Hz), 7.65 (d, 1H, J=2.1 Hz), 7.34-7.38 (m, 3H), 4.60 (t, 1H, J=5.7 Hz),3.22-3.40 (m, 4H), 3.19 (s, 3H), 1.81 (d, 3H, J=1.5 Hz), 1.66-1.85 (m,2H), 1.38-1.64 (m, 4H), 1.21-1.29 (m, 4H), 0.84 (t, 3H, J=6.6 Hz).

Example 133 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-3,3-dimethylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B54)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.94-8.03 (m, 3H), 7.66 (d, 1H, J=2.5Hz), 7.30-7.41 (m, 3H), 4.65 (dd, 1H, J=8.8 Hz, 3.0 Hz), 3.15 (s, 3H),1.81 (d, 3H, J=1.6 Hz), 1.73 (dd, 1H, J=14.4 Hz, 8.6 Hz), 1.45 (dd, 1H,J=14.4 Hz, 2.8 Hz), 0.97 (s, 9H).

Example 134 Synthesis of3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-3-n-butyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B55)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.94-8.06 (m, 3H), 7.66 (d, 1H, J=2.7Hz), 7.35-7.41 (m, 3H), 4.68-4.73 (m, 1H), 3.34-3.54 (m, 4H), 3.19 (s,3H), 1.85-2.01 (m, 2H), 1.81 (d, 3H, J=1.6 Hz), 1.41-1.50 (m, 2H),1.25-1.37 (m, 2H), 086 (t, 3H, J=7.2 Hz).

Example 135 Synthesis of3-(2,6-dichloro-4-{4-[3-(1-ethyloxy-2,2-dimethylpropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B56)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.02 (m, 1H), 7.62 (d, 1H,J=2.3 Hz), 7.41 (s, 1H), 7.30-7.40 (m, 2H), 4.42 (s, 1H), 3.20-3.40 (m,2H), 1.69 (s, 3H), 1.11 (t, 3H, J=7.0 Hz), 0.91 (s, 9H).

Example 136 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(4-methyloxy-4-heptyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B57)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.98 (t, 1H, J=7.3 Hz),7.62, (d, 1H, J=2.4 Hz), 7.51 (t, 1H, J=7.0 Hz), 7.40 (d, 1H, J=1.2 Hz),7.27 (t, 1H, J=7.8 Hz), 3.17 (s, 3H), 1.80-2.00 (m, 4H), 1.69 (d, 3H,J=1.2 Hz), 0.75-1.35 (m, 10H).

Example 137 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B58)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.02 (m, 1H), 7.65 (d, 1H,J=2.5 Hz), 7.30-7.44 (m, 3H), 4.57 (t, 1H, J=6.8 Hz), 3.18 (s, 3H), 1.69(d, 3H, J=1.1 Hz), 1.20-1.83 (m, 8H), 0.84 (t, 3H, J=6.1 Hz).

Example 138 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methyloxy-2,4-dimethylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B59)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.30 (s, 2H), 8.03 (m, 1H), 7.56 (d, 1H,J=3.1 Hz), 7.30-7.44 (m, 3H), 3.33 (s, 3H), 2.50-2.70 (m, 2H), 1.69 (d,3H, J=1.2 Hz), 0.90 (d, 12H, J=6.7 Hz).

Example 139 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B60)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 8.29 (d, 2H, J=1.2 Hz), 8.03 (m, 1H),7.66 (d, 1H, J=0.9 Hz), 7.31-7.45 (m, 3H), 4.55 (t, 1H, J=6.3 Hz), 3.18(d, 3H, J=1.2 Hz), 1.69 (s, 3H), 1.10-1.85 (m, 5H), 0.85 (d, 6H, J=6.7Hz).

Example 140 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B61)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 8.29 (s, 2H), 8.02 (m, 1H), 7.64 (d, 1H,J=1.5 Hz), 7.29-7.45 (m, 3H), 4.56 (t, 1H, J=6.4 Hz), 3.18 (s, 3H), 1.69(s, 3H), 1.15-1.85 (m, 16H), 0.83 (t, 3H, J=6.6 Hz).

Example 141 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-ethyloxy-3,3-dimethylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B62)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.00 (dt, 1H, J=1.8, 7.6Hz), 7.65 (d, 1H, J=2.4 Hz), 7.29-7.45 (m, 3H), 4.77 (dd, 1H, J=2.4, 8.8Hz), 3.25-3.40 (m, 2H), 1.69 (s, 3H), 1.68 (m, 1H), 1.43 (dd, 1H, J=2.4,14.3 Hz), 1.12 (t, 3H, J=6.9 Hz), 0.919 (s, 9H).

Example 142 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methyloxy-1-n-pentyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B63)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.35 (s, 1H), 8.16 (d, 1H, J=9.9 Hz),8.00-8.08 (m, 3H), 7.65 (d, 1H, J=2.4 Hz), 7.31-7.42 (m, 2H), 4.82 (q,1H, J=4.2 Hz), 3.10-3.50 (m, 2H), 2.58 (t, 2H, J=7.5 Hz), 2.06 (s, 3H),1.82-2.02 (m, 2H), 1.46-1.58 (m, 2H), 1.20-1.36 (m, 4H), 0.85 (t, 3H,J=6.9 Hz).

Example 143 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B64)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 8.03 (dt, 1H, J=7.0 Hz,2.2 Hz), 7.62 (d, 1H, J=2.5 Hz), 7.28-7.41 (m, 3H), 4.32 (s, 1H), 3.15(s, 3H), 1.69 (d, 3H, J=1.3 Hz), 0.91 (s, 9H).

Example 144 Synthesis of3-[2,6-dichloro-4-(4-{3-[1-(4-ethyloxybutyloxy)propyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B65)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 8.29 (s, 2H), 8.01 (t, 1H, J=6.0 Hz),7.64 (d, 1H, J=2.1 Hz), 7.40 (s, 1H), 7.30-7.37 (m, 2H), 4.59 (t, 1H,J=6.0 Hz), 3.00-3.70 (m, 6H), 1.60-1.86 (m, 2H), 1.69 (s, 3H), 1.41-1.63(m, 4H), 1.07 (t, 3H, J=6.9 Hz), 0.89 (t, 3H, J=6.9 Hz).

Example 145 Synthesis of3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B66)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.2 Hz), 7.63 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.5 Hz), 7.21-7.32 (m,2H), 3.42 (t, 2H, J=6.0 Hz), 3.04 (s, 2H), 2.76 (t, 2H, J=7.2 Hz),1.80-1.91 (m, 2H), 1.69 (d, 3H, J=1.2 Hz), 0.89 (s, 9H).

Example 146 Synthesis of3-[2,6-dichloro-4-(4-{3-[1-n-pentyloxypropyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B67)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.4 Hz,6.9 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.31-7.40 (m, 3H), 4.59 (t, 1H, J=6.9Hz), 3.20-3.42 (m, 2H), 1.69 (d, 3H, J=1.5 Hz), 1.64-1.81 (m, 2H),1.46-1.56 (m, 2H), 1.23-1.34 (m, 4H), 0.89 (t, 3H, J=7.2 Hz), 0.85 (t,3H, J=7.2 Hz).

Example 147 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyheptyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B68)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.29 (d, 2H, J=0.9 Hz), 8.03 (t, 1H,J=7.3), 7.64 (d, 1H, J=2.3 Hz), 7.31-7.40 (m, 3H), 4.56 (t, 1H, J=6.5Hz), 3.18 (s, 3H), 1.60-1.80 (m, 4H), 1.70 (d, 3H, J=1.3 Hz), 1.20-1.30(m, 6H), 0.81-0.85 (m, 3H).

Example 148 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyoctyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B69)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (d, 2H, J=0.9 Hz), 7.99-8.10 (m,1H), 7.64 (d, 1H, J=1.3 Hz), 7.31-7.40 (m, 3H), 4.56 (t, 1H, J=6.5 Hz),3.18 (s, 3H), 1.69 (d, 3H, J=1.3 Hz), 1.58-1.84 (m, 2H), 1.16-1.0 (m,10H), 0.81-0.85 (m, 3H).

Example 149 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-pentyloxypentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B70)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 8.00 (dt, 1H, J=7.4 Hz,2.2 Hz), 7.64 (d, 1H, J=2.5 Hz), 7.30-7.40 (m, 3H), 4.64 (dt, 1H, J=1.6Hz, 5.5 Hz), 3.28 (t, 2H, J=6.6 Hz), 1.69 (d, 3H, J=1.3 Hz), 1.62-1.73(m, 2H), 1.45-1.52 (m, 2H), 1.22-1.33 (m, 8H), 0.82-0.87 (m, 6H).

Example 150 Synthesis of3-(2,6-dichloro-4-{4-[3-(1-ethyloxypentyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B71)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 1H), 8.00 (dt, 1H, J=7.3 Hz,2.2 Hz), 7.64 (d, 1H, J=2.5 Hz), 7.30-7.40 (m, 3H), 4.67 (t, 1H, J=6.6Hz), 3.35 (q, 2H, J=6.9 Hz), 1.63-1.73 (m, 5H), 1.27-1.33 (m, 4H), 1.12(t, 3H, J=6.9 Hz), 0.83-0.87 (m, 3H).

Example 151 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxynonyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B72)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (m, 1H), 7-65 (d, 1H,J=2.4 Hz), 7.41 (d, 1H, J=1.2 Hz), 7.32-7.38 (m, 2H), 4.52 (t, 1H, J=6.6Hz), 3.20 (s, 3H), 1.68-1.84 (m, 5H), 1.18-1.40 (m, 12H), 0.87 (t, 3H,J=7.2 Hz).

Example 152 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methyloxyoctyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B73)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.93 (dt, 1H, J=1.8 Hz,7.5 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.2 Hz), 7.20-7.31 (m,2H), 3.25 (s, 3H), 3.19 (m, 1H), 2.62-2.80 (m, 2H), 1.72-1.77 (m, 2H),1.69 (d, 3H, J=1.2 Hz), 1.40-1.54 (m, 2H), 1.20-1.38 (m, 6H), 0.86 (t,3H, J=6.6 Hz).

Example 153 Synthesis of3-[2,6-dichloro-4-(4-{2-fluoro-3-[1-(3-methylbutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B74)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.4 Hz,6.9 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.40 (t, 1H, J=1.5 Hz), 7.31-7.38 (m,2H), 4.59 (t, 1H, J=6.0 Hz), 3.12-3.43 (m, 2H), 1.63-1.81 (m, 3H),1.37-1.44 (m, 2H), 0.89 (t, 3H, J=7.2 Hz), 0.86 (t, 3H, J=6.6 Hz), 0.82(t, 3H, J=6.6 Hz).

Example 154 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-octyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B75)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=7.5 Hz,2.0 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.38-7.42 (m, 1H), 7.32 (t, 2H, J=7.7Hz), 4.79 (q, 1H, J=6.7 Hz), 3.23-3.40 (m, 2H), 1.69 (s, 3H), 1.45-1.40(m, 2H), 1.41 (d, 3H, 6.4 Hz), 1.22-1.30 (m, 8H), 0.81-0.86 (m, 3H).

Example 155 Synthesis of3-{2,6-dichloro-4-[4-(3-n-decyloxymethyl-2-fluorophenyl)thiazol-Z-ylcarbamoyl]phenyl}-2-methylacrylicacid (B76)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=7.7 Hz,1.3 Hz), 7.64 (d, 1H, J=2.5 Hz), 7.38-7.45 (m, 2H), 7.31 (t, 1H, J=7.7Hz), 4.58 (s, 2H), 3.48 (t, 2H, 6.5 Hz), 1.69 (s, 3H), 1.49-1.58 (m,2H), 1.22-1.33 (m, 14H), 0.82-0.86 (m, 3H).

Example 156 Synthesis of3-{2,6-dichloro-4-[4-(2-fluoro-3-{n-pentyloxymethyl}phenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B77)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=7.5 Hz,1.8 Hz), 7.66 (d, 1H, J=2.4 Hz), 7.40-7.46 (m, 2H), 7.31 (t, 1H, J=7.6Hz), 4.58 (s, 2H), 3.49 (t, 2H, 6.4 Hz), 1.69 (d, 3H, J=1.5 Hz),1.52-1.60 (m, 2H), 1.28-1.33 (m, 4H), 0.84-0.89 (m, 3H).

Example 157 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-propyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B78)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.29 (d, 2H, J=0.9 Hz), 8.03 (t, 1H,J=−7.3), 7.64 (d, 1H, J=2.3 Hz), 7.31-7.40 (m, 3H), 4.67 (t, 1H, J=6.5Hz), 3.21 (t, 2H, J=6.5), 1.66 (d, 3H, J=1.3 Hz), 1.30-1.84 (m, 6H),0.81-0.85 (m, 6H).

Example 158 Synthesis of3-(4-{4-[3-(1-n-butyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B-79)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.27 (d, 2H, J=0.9 Hz), 8.00 (t, 1H,J=7.4), 7.63 (d, 1H, J=2.3 Hz), 7.31-7.38 (m, 3H), 4.67 (t, 1H, J=6.4Hz), 3.21 (t, 2H, J=6.5), 1.69 (d, 3H, J=1.3 Hz), 1.20-1.84 (m, 8H),0.81-0.85 (m, 6H).

Example 159 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-pentyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B80)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.28 (d, 2H, J=0.9 Hz), 8.00 (t, 1H,J=7.4), 7.63 (d, 1H, J=2.3 Hz), 7.31-7.38 (m, 3H), 4.65 (t, 1H, J=6.4Hz), 3.21 (t, 2H, J=6.5), 1.70 (d, 3H, J=1.3 Hz), 1.20-1.70 (m, 10H),0.81-0.85 (m, 6H).

Example 160 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B81)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.1 Hz,7.2 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.31-7.43 (m, 3H), 4.60 (t, 1H, J=6.3Hz), 3.21-3.40 (m, 3H), 1.69 (d, 3H, J=1.2 Hz), 1.64-1.82 (m, 2H),1.47-1.59 (m, 2H), 0.89 (t, 3H, J=7.5 Hz), 0.88 (t, 3H, J=7.2 Hz).

Example 161 Synthesis of3-(4-{4-[3-(1-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B82)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.1 Hz,7.2 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.5 Hz), 7.31-7.38 (m,2H), 4.59 (t, 1H, J=6.6 Hz), 3.24-0.37 (m, 2H), 1.69 (d, 3H, J=1.2 Hz),1.45-1.55 (m, 2H), 1.28-1.40 (m, 4E), 0.89 (t, 3H, J=7.5 Hz), 0.86 (t,3H, J=7.2 Hz).

Example 162 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-hexyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B83)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.7 Hz,6.9 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.30-7.40 (m, 3H), 4.59 (t, 1H, J=6.6Hz), 3.25-3.39 (m, 2H), 1.64-1.81 (m, 2H), 1.69 (d, 3H, J=1.2 Hz),1.49-1.56 (m, 2H), 1.16-1.36 (m, 6H), 0.89 (t, 3H, J=7.2 Hz), 0.84 (t,3H, J=6.6 Hz).

Example 163 Synthesis of3-[2,6-dichloro-4-(4-[2-fluoro-3-[3-(4-methylpentyloxy)propyl]phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B84)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.2 Hz), 7.63 (d, 1H, J=2.4 Hz), 7.40 (d, 1H, J=1.2 Hz), 7.21-7.30 (m,2H), 3.32-3.41 (m, 4H), 2.74 (t, 2H, J=7.8 Hz), 1.78-1.88 (m, 2H), 1.69(d, 3H, J=1.5 Hz), 1.45-1.56 (m, 3H), 1.14-1.22 (m, 2H), 0.86 (d, 6H,J=6.6 Hz).

Example 164 Synthesis of3-[2,6-dichloro-4-(4-[3-[3-(3,3-dimethylbutyloxy)propyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B85)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=1.8 Hz,7.8 Hz), 7.63 (d, 1H, J=2.4 Hz), 7.41 (s, 1H), 7.21-7.30 (m, 2H),3.25-3.48 (m, 4H), 2.74 (t, 2H, J=7.5 Hz), 1.78-1.87 (m, 2H), 1.69 (d,3H, J=1.2 Hz), 1.44 (t, 2H, J=7.5 Hz), 0.90 (s, 9H).

Example 165 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-propyloxypentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B86)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00 (dt, 1H, J=7.5 Hz,2.0 Hz), 7.64 (d, 1H, J=2.5 Hz), 7.30-7.41 (m, 3H), 4.63-4.67 (m, 1H),3.25 (t, 2H, 6.4 Hz), 1.64-1.78 (m, 5H), 1.52 (q, 2H, J=6.9 Hz),1.28-1.33 (m, 4H), 0.84-0.90 (m, 6H).

Example 166 Synthesis of3-(4-{4-[3-(1-n-butyloxypentyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B87)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00 (dt, 1H, J=7.5 Hz,2.2 Hz), 7.64-7.65 (m, 1H), 7.30-7.41 (m, 3H), 4.62-4.67 (m, 1H), 3.29(t, 2H, 6.4 Hz), 1.60-1.80 (m, 5H), 1.45-1.54 (m, 2H), 1.28-1.40 (m,6H), 0.82-0.88 (m, 6H).

Example 167 Synthesis of3-[2,6-dichloro-4-(4-[3-[3-(2-ethylbutyloxy)propyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B88)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.5 Hz), 7.63 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.5 Hz), 7.21-7.30 (m,2H), 3.40 (t, 2H, J=6.3 Hz), 3.26 (d, 2H, J=5.4 Hz), 2.74 (t, 2H, J=7.2Hz), 1.74-1.91 (m, 2H), 1.69 (d, 3H, J=1.5 Hz), 1.20-1.42 (m, 5H), 0.85(t, 6H, J=7.8 Hz).

Example 168 Synthesis of3-[2,6-dichloro-4-(4-[3-[3-(2-cyclopentylethyloxy)propyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B89)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.2 Hz), 7.63 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.5 Hz), 7.20-7.30 (m,2H), 3.20-3.46 (m, 4H), 2.74 (t, 2H, J=7.8 Hz), 1.60-1.90 (m, 4H), 1.69(d, 3H, J=1.5 Hz), 1.44-1.59 (m, 5H), 1.02-1.15 (m, 4H).

Example 169 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-n-pentyloxy)propyl]phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B90)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.1 Hz,6.6 Hz), 7.63 (d, 1H, J=2.4 Hz), 7.40 (s, 1H), 7.21-7.30 (m, 2H),3.33-3.42 (m, 4H), 2.74 (t, 2H, J=7.5 Hz), 1.78-1.88 (m, 2H), 1.69 (d,3H, J=1.2 Hz), 1.44-1.57 (m, 2H), 1.26-1.31 (m, 4H), 0.87 (t, 3H, J=7.2Hz).

Example 170 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyundecyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B91)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.99-8.05 (m, 1H), 7.64(s, 1H), 7.30-7.40 (m, 3H), 4.56 (t, 1H, J=6.5 Hz), 3.18 (s, 3H),1.60-1.80 (m, 5H), 1.14-1.36 (m, 16H), 0.81-0.85 (m, 3H).

Example 171 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxydodecyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B92)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00-8.05 (m, 1H), 7.64(d, 1H, J=2.7 Hz), 7.31-7.41 (m, 3H), 4.56 (t, 1H, J=6.4 Hz), 3.18 (s,3H), 1.60-1.80 (m, 51), 1.20-1.36 (m, 18H), 0.81-0.85 (m, 3H).

Example 172 Synthesis of3-(4-{4-[3-(3-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl]-2-methylacrylicacid (B93)

1H-NMR(DMSO-d6) 13.04 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.2 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.2 Hz), 7.21-7.32 (m,2H), 3.20-3.42 (m, 4H), 2.74 (t, 2H, J=8.1 Hz), 1.78-1.88 (m, 2H), 1.69(d, 3H, J=1.2 Hz), 1.44-1.53 (m, 2H), 1.27-1.39 (m, 2H), 0.88 (t, 3H,J=6.9 Hz).

Example 173 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isopropyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B94)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.4 Hz,7.2 Hz), 7.64 (d, 1H, J=2.7 Hz), 7.41 (d, 1H, J=1.2 Hz), 7.21-7.31 (m,2H), 3.52 (m, 1H), 3.35-3.41 (m, 2H), 2.74 (t, 2H, J=8.1 Hz), 1.76-1.85(m, 2H), 1.69 (d, 3H, J=1.8 Hz), 1.09 (d, 6H, J=6.3 Hz).

Example 174 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-n-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B95)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8-29 (s, 2H), 7.94 (dt, 1H, J=1.8 Hz,7.2 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.41 (1, 1H), 7.21-7.31 (m, 2H),3.30-3.42 (m, 4H), 2.74 (t, 2H, J=7.8 Hz), 1.78-1.88 (m, 2H), 1.69 (s,3H), 1.49-1.58 (m, 2H), 0.88 (t, 3H, J=7.5 Hz).

Example 175 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-n-hexyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B96)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.93 (dt, 1H, J=2.7 Hz,7.8 Hz), 7.63 (d, 1H, J=2.4 Hz), 7.41 (d, 1H, J=1.5 Hz), 7.21-7.31 (m,2H), 3.20-3.45 (m, 4H), 2.74 (t, 2H, J=7.5 Hz), 1.78-1.87 (m, 2H), 1.69(d, 3H, J=1.8 Hz), 1.44-1.53 (m, 2H), 1.21-1.36 (m, 6H), 0.86 (t, 3H,J=6.9 Hz).

Example 176 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-propyloxyethyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B97)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=7.6 Hz,1.8 Hz), 7.65 (d, 1H, J=2.4 Hz), 7.31-7.45 (m, 3H), 4.80 (t, 1H, J=6.4Hz), 3.20-3.39 (m, 2H), 1.69 (d, 3H, J=1.5 Hz), 1.52 (qint, 2H, J=7.0Hz), 1.41 (d, 3H, J=6.4 Hz), 0.87 (t, 3H, J=7.3 Hz).

Example 177 Synthesis of3-(4-{4-[3-(1-n-butyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl)-2,6-dichlorophenyl]-2-methylacrylicacid (B98)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=7.3 Hz,1.8 Hz), 7.65 (d, 1H, J=2.4 Hz), 7.39-7.44 (m, 1H), 7.34 (t, 2H, J=7.6Hz), 4.80 (q, 1H, J=6.4 Hz), 3.25-3.41 (m, 2H), 1.69 (d, 3H, J=1.2 Hz),1.45-1.55 (m, 2H), 1.41 (d, 3H, J=6.4 Hz), 1.29-1.37 (m, 2H), 0.86 (t,3H, J=7.3 Hz).

Example 178 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-n-hexyloxyethyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B99)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.00 (dt, 1H, J=7.5 Hz,1.9 Hz), 7.64 (d, 1H, J=2.5 Hz), 7.31-7.43 (m, 3H), 4.80 (q, 1H, J=6.4Hz), 3.23-3.40 (m, 2H), 1.69 (d, 3H, J=1.4 Hz), 1.46-1.53 (m, 2H), 1.41(d, 3H, J=6.4 Hz), 1.20-1.35 (m, 6H), 0.82-0.87 (m, 3H).

Example 179 Synthesis of3-(4-{4-[3-(1,4-dibutyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl)-2,6-dichlorophenyl]-2-methylacrylicacid (B100)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01 (dt, 1H, J=2.1 Hz,6.8 Hz), 7.64 (d, 1H, J=2.4 Hz), 7.41 (d, 1H, J=1.5 Hz), 7.31-7.38 (m,2H), 4.68 (t, 3H, J=6.2 Hz), 3.16-3.20 (m, 6H), 1.69 (d, 3H, J=1.5 Hz),1.55-1.75 (m, 4H), 1.40-1.54 (m, 4H), 1.25-1.37 (m, 4H), 0.86 (dt, 6H,J=1.2 Hz, 6.9 Hz).

Example 180 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-n-hexyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B101)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.03 (dt, 1H, J=2.1 Hz,6.6 Hz), 7.65 (d, 1H, J=2.7 Hz), 7.32-7.41 (m, 3H), 4.71 (m, 1H,),3.25-3.40 (m, 4H), 3.18 (s, 3H), 1.83-2.01 (m, 2H), 1.69 (s, 3H),1.40-1.50 (m, 2H), 1.18-1.32 (m, 6H), 0.85 (t, 3H, J=6.9Hz).

Example 181 Synthesis of(Z)-3-(4-{4-[3-(4-methylpentyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B121)

1H-NMR(DMSO-d6) 13.56 (bs, 1H), 12.96 (bs, 1H), 7.89-7.96 (m, 3H), 7.63(d, 1H, J=2.6 Hz), 7.20-7.31 (m, 2H), 6.66 (s, 1H), 3.71 (s, 3H), 2.67(t, 2H, J=7.6 Hz), 1.53-1.62 (m, 3H), 1.20-1.27 (m, 2H), 0.88 (d, 6H,J=6.6 Hz).

Example 182 Synthesis of(Z)-3-(4-{4-[3-(3,3-dimethylbutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl]-2-methyloxyacrylicacid (B122)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00-8.06 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.31-7.41 (m, 3H), 4.69-4.74 (m, 1H), 3.48-3.55 (m,1H), 3.25-3.40 (m, 3H), 1.86-2.03 (m, 2H), 1.69 (s, 3H), 1.43-1.54 (m,2H), 0.83-0.88 (m, 3H).

Example 183 Synthesis of(E)-3-(4-{4-[3-(3,3-dimethylbutyl)-2-methoxyphenyl]thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B134)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.92-8.00 (m, 2H), 7.84 (dd, 1H, J=1.8,6.9 Hz), 7.72 (s, 1H), 7.33 (s, 1H), 7.12-7.23 (m, 2H), 3.62 (s, 3H),2.60-2.65 (m, 2H), 1.81 (s, 3H), 1.45-1.51 (m, 2H), 0.98 (s, 9H).

Example 184 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B169)

1H-NMR(DMSO-d6) 13.20 (bs, 1H), 12.99 (bs, 1H), 8.25 (s, 2H), 7.90-7.96(m, 1H), 7.62-7.63 (m, 1H), 7.20-7.30 (m, 2H), 6.73 (s, 1H), 3.61 (s,3H), 2.67 (t, 2H, J=7.6 Hz), 1.53-1.66 (m, 3H), 1.20-1.27 (m, 2H), 0.88(d, 6H, J=6.6 Hz).

Example 185 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B170)

1H-NMR(DMSO-d6) 13.51 (bs, 1H), 13.00 (bs, 1H), 8.25 (s, 2H), 7.89-7.95(m, 1H), 7.63 (d, 1H, J=2.6 Hz), 7.19-7.31 (m, 2H), 6.73 (s, 1H), 3.62(s, 3H), 2.62-2.68 (m, 2H), 1.45-1.50 (m, 2H), 0.97 (s, 9H).

Example 186 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B195)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.92-8.08 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.30-7.41 (m, 3H), 4.52 (t, 1H, J=6.3 Hz), 3.20 (s, 3H), 1.65-1.85(m, 5H), 0.87 (t, 3H, J=7.2 Hz).

Example 187 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B216)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.92-8.05 (m, 3H), 7.64 (d, 1H, J=2.7Hz), 7.30-7.42 (m, 3H), 4.60 (t, 1H, J=6.6 Hz), 3.10-3.42 (m, 2H),1.65-1.86 (m, 5H), 1.47-1.59 (m, 2H), 0.85-0.92 (m, 6H).

Example 188 Synthesis of(E)-3-(4-{4-[3-(cyclohexylpropyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B233)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.04 (m, 3H), 7.64 (d, 1H, J=2.6Hz), 7.32-7.35 (m, 3H), 4.40 (d, 1H, J=7.0 Hz), 3.17-3.23 (m, 2H),1.93-1.97 (m, 1H), 1.04-1.64 (m, 12H), 0.86 (t, 3H, J=7.5 Hz).

Example 189 Synthesis of(E)-3-(4-{4-[3-(1-butyloxy-2,2-dimethylpropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B255)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 7.95-8.05 (m, 3H), 7.61-7.62 (m, 1H),7.32-7.34 (m, 3H), 4.39 (s, 1H), 3.22 (t, 2H, J=6.3 Hz), 1.81 (s, 3H),1.33-1.51 (m, 4H), 0.84-0.91 (m, 12H).

Example 190 Synthesis of(E)-3-(4-{4-[3-(butyloxycyclohexylmethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B264)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.04 (m, 3H), 7.64 (d, 1H, J=2.6Hz), 7.32-7.34 (m, 3H), 4.39 (d, 1H, J=7.0 Hz), 3.22-3.27 (m, 2H),1.93-1.97 (m, 1H), 1.04-1.64 (m, 14H), 0.86 (t, 3H, J=7.5 Hz).

Example 191 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B347)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.90-8.00 (m, 3H), 7.72 (s, 1H),7.24-7.45 (m, 3H), 4.56-4.60 (m, 1H), 3.62 (s, 3H), 3.16 (s, 3H), 1.81(s, 3H), 1.20-1.78 (m, 8H), 0.83-0.88 (m, 3H).

Example 192 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxy-5-methylhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B348)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.89-7.97 (m, 3H), 7.72 (s, 1H),7.24-7.34 (m, 3H), 4.53-4.57 (m, 1H), 3.61 (s, 3H), 3.16 (s, 3H), 1.81(s, 3H), 0.87-1.72 (m, 13H).

Example 193 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxy-3,3-dimethylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B349)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.92-8.00 (m, 2H), 7.89 (dd, 1H, J=1.8,7.5 Hz), 7.71 (s, 1H), 7.31-7.36 (m, 2H), 7.25 (t, 1H, J=7.8 Hz), 4.69(d, 1H, J=7.8 Hz), 3.63 (s, 3H), 3.13 (s, 3H), 1.81 (s, 3H), 1.63-1.71(m, 1H), 1.40 (d, 1H, J=14.4 Hz), 1.00 (s, 9H)I.

Example 194 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B354)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.90-8.00 (m, 3H), 7.72 (s, 1E),7.24-7.36 (m, 3H), 4.55 4.59 (m, 1H), 3.61 (s, 3H), 3.16 (s, 3H), 1.81(s, 3H), 1.50-1.78 (m, 2H), 1.16-1.50 (m, 14H), 0.82-0.87 (m, 3H).

Example 195 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxyundecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B355)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.90-8.00 (m, 3H), 7.73 (s, 1H),7.24-7.36 (m, 3H), 4.56-4.59 (m, 1H), 3.61 (s, 3H), 3.15 (s, 3H), 1.81(s, 3H), 1.50-1.78 (m, 2H), 1.16-1.50 (m, 16H), 0.82-0.87 (m, 3H).

Example 196 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B380)

1H-NMR(CDCl₃-d6) 7.90 (s, 1H), 7.87 (s, 1H), 7.58 (s, 1H), 7.48-7.52 (m,1H), 7.46 (s, 1H), 7.25-7.30 (m, 1H), 7.18 (t, 1H, J=7.5 Hz), 3.58 (s,3H), 3.50 (t, 2H, J=6.3 Hz), 3.41 (t, 2H, J=6.6 Hz), 2.80 (t, 2H, J=8.4Hz), 1.91-2.02 (m, 5H), 1.63 (q, 2H, J=7.2 Hz), 0.95 (t, 3H, J=7.5 Hz).

Example 197 Synthesis of(E)-3-(4-{4-[3-(cyclohexylpropyloxymethyl-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B397)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.92-8.00 (m, 2H), 7.89 (dd, 1H, J=1.8,6.9 Hz), 7.71 (s, 1H), 7.34 (s, 1H), 7.22-7.31 (m, 2H), 4.40 (d, 1H,J=6.9 Hz), 3.59 (s, 3H), 3.06-3.25 (m, 2H), 1.90-2.00 (m, 1H), 1.81 (s,3H), 1.44-1.76 (m, 6H), 1.36-1.28 (m, 1H), 1.00-1.20 (m, 5H), 0.87 (t,3H, J=7.2 Hz).

Example 198 Synthesis of(E)-3-(4-{4-[3-(1-butyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B418)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 7.89-8.05 (m, 3H), 7.72 (s, 1H),7.31-7.36 (m, 2H), 7.26 (t, 1H, J=7.8 Hz), 4.55-4.63 (m, 1H), 3.61 (s,3H), 1.81 (s, 3H), 1.62-1.76 (m, 2H), 1.43-1.55 (m, 2H), 1.28-1.41 (m,2H), 0.84-0.95 (m, 6H).

Example 199 Synthesis of(E)-3-(4-{4-[3-(3-butyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B419)

1H-NMR(CDCl₃-d6) 7.91 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.49 (d, 1H,J=7.5 Hz), 7.46 (s, 1H), 7.25-7.29 (m, 1H), 7.17 (t, 1H, J=7.8 Hz), 3.58(s, 3H), 3.50 (t, 1H, J=6.6 Hz), 3.45 (t, 1H, J=6.9 Hz), 2.80 (t, 2H,J=8.4 Hz), 1.90-2.02 (m, 5H), 1.53-1.64 (m, 2H), 1.34-1.48 (m, 2H), 0.94(t, 3H, J=7.2 Hz).

Example 200 Synthesis of(E)-3-(4-{4-[3-(1-butyloxy-2,2-dimethylpropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B425)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.88-8.10 (m, 3H), 7.70 (s, 1H), 7.34(s, 1H), 7.22-7.31 (m, 2H), 4.40 (s, 1H), 3.57 (s, 3H), 1.81 (s, 3H),1.32-1.55 (m, 4H), 0.85-0.92 (m, 12H).

Example 201 Synthesis of(E)-3-(4-{4-[3-(cyclohexylpentyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B484)

1H-NMR(DMSO-D6) 12-98 (bs, 2H), 7.92-8.00 (m, 2H), 7.86-7.95 (m, 1H),7.70 (s, 1H), 7.34 (s, 1H), 7.22-7.30 (m, 2H), 4.39 (d, 1H, J=7.2 Hz),3.59 (s, 3H), 3.21-3.28 (m, 2H), 1.88-2.00 (m, 1H), 1.81 (s, 3H),1.44-1.78 (m, 6H), 1.00-1.36 (m, 101), 0.83-0.87 (m, 3H).

Example 202 Synthesis of(E)-3-(4-{4-[3-(2,2-dimethylpropyloxy)propyl]-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B488)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.92-8.00 (m, 2H), 7.84-7.90 (m, 1H),7.73 (s, 1H), 7.34 (s, 1H), 7.14-7.25 (m, 2H), 3.62 (s, 3H), 3.45 (t,2H, J=6.3 Hz), 3.06 (s, 2H), 2.74 (t, 2H, J=6.3 Hz), 1.81-1.90 (m, 5H),1.90 (s, 9H).

Example 203 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-(3-hexyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B505)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.92-8.00 (m, 2H), 7.86 (dd, 1H, J=1.5,7.5 Hz), 7.72 (s, 1H), 7.34 (s, 1H), 7.23 (dd, 2H, J=1.5, 7.5 Hz), 7.16(t, 1H, J=7.5 Hz), 3.61 (s, 3H), 3.20-3.46 (m, 4H), 2.69-2.74 (m, 2H),1.76-1.88 (m, 5H), 1.46-1.56 (m, 2H), 1.20-1.38 (m, 6H), 1.84-0.89 (m,3H).

Example 204 Synthesis of(E)-3-(4-{4-[3-(cyclohexylhexyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B519)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.92-8.00 (m, 2H), 7.89 (dd, 1H, J=2.7,7.5 Hz), 7.70 (s, 1H), 7.34 (s, 1H), 7.22-7.29 (m, 2H), 4.39 (d, 1H,J=7.2 Hz), 3.59 (s, 3H), 1.90-2.00 (m, 1H), 1.81 (s, 3H), 1.02-1.76 (m,16H), 1.32-1.55 (m, 4H), 0.85 (t, 3H, J=6.9 Hz).

Example 205 Synthesis of(E)-3-[4-(4-{3-[3-(3,3-dimethylbutyloxy)propyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B521)

1H-NMR(CDCl₃-d6) 7.91 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.43-7.54 (m,2H), 7.25-7.30 (m, 1H), 7.17 (t 1H, J=7.5 Hz), 3.58 (s, 3H), 3.46-3.52(m, 4H), 2.80 (t, 2H, J=8.1 Hz), 1.90-2.30 (m, 5H), 1.54 (t, 2H, J=7.5Hz), 0.94 (s, 9H).

Example 206 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B533)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.00-8.05 (m, 1H), 7.89-7.95 (m, 2H),7.65 (d, 1H, J=2.4 Hz), 7.31-7.39 (m, 2H), 6.67 (s, 1H), 4.55-4.59 (m,1H), 3.72 (s, 3H), 3.18 (s, 3H), 1.64-1.76 (m, 2H), 1.26-1.41 (m, 6H),0.81-0.86 (m, 3H).

Example 207 Synthesis of(Z)-3-(4-{4-[3-(3-butyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B790)

1H-NMR(CDCl3-d6) 7.83 (s, 1H), 7.80 (s, 1H), 7.48 (d, 1H, J=7.8 Hz),7.44 (s, 1H), 7.26-7.30 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 6.91 (s, 1H),3.90 (s, 3H), 3.58 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 3.44 (t, 2H, J=6.3Hz), 2.80 (t, 2H, J=8.1 Hz), 1.91-2.05 (m, 2H), 1.53-1.63 (m, 2H),1.34-1.46 (m, 2H), 0.94 (t, 3H, J=7.5 Hz).

Example 208 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B896)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.95-8.06 (m, 1H), 7.65(d, 1H, J=2.4 Hz), 7.32-7.42 (m, 3H), 4.52 (t, 1H, J=6.3 Hz), 3.20 (s,3H), 1.66-1.84 (m, 5H), 0.87 (t, 1H, J=7.5 Hz).

Example 209 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B897)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00-8.06 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.31-7.41 (m, 3H), 4.69-4.74 (m, 1H), 3.48-3.55 (m,1H), 3.25-3.40 (m, 3H), 1.86-2.03 (m, 2H), 1.69 (s, 3H), 1.43-1.54 (m,2H), 0.83-0.88 (m, 3H).

Example 210 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-4-pentyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B899)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.97-8.06 (m, 1H), 7.64(d, 1H, J=2.4 Hz), 7.31-7.40 (m, 3H), 4.60 (t, 1H, J=6.0 Hz), 3.19 (s,3H), 1.66-1.82 (m, 5H), 1.41-1.65 (m, 4H), 1.22-1.30 (m, 4H), 0.81-0.86(m, 3H).

Example 211 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-3,3-dimethylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B905)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.97-8.03 (m, 1H), 7.65(d, 1H, J=2.5 Hz), 7.30-7.40 (m, 3H), 4.64-4.68 (m, 1H), 3.25 (s, 3H),1.69-1.77 (m, 4H), 1.42-1.48 (m, 1H), 0.97 (s, 9H).

Example 208 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2,2-dimethyl-1-propyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid (B927)

1H-NMR(DMSO-d6) 13.00 (s, 2H), 8.30 (s, 2H), 7.99-8.04 (m, 1H),7.61-7.62 (m, 1H), 7.32-7.41 (m, 3H), 4.40 (s, 1H), 3.16-3.33 (m, 2H),169 (s, 3H), 1.47-1.55 (m, 2H), 0.84-0.91 (m, 12H).

Example 213 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(cyclohexylpropyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B936)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.30 (s, 1H), 7.98-8.03 (m, 1H), 7.63(d, 1H, J=2.3 Hz), 7.32-7.40 (m, 3H), 4.40 (d, 1H, J=7.0 Hz), 3.18-3.23(m, 2H), 1.93-1.97 (m, 1H), 1.04-1.64 (m, 12H), 0.86 (t, 3H, J=7.5 Hz).

Example 214 Synthesis of(E)-3-(4-{4-[3-(1-butyloxy-2,2-dimethylpropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B958)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.99-8.04 (m, 1H),7.61-7.62 (m, 1H), 7.32-7.41 (m, 3H), 4.40 (s, 1H), 3.32 (t, 2H, J=6.3Hz), 169 (s, 3H), 1.29-1.53 (m, 4H), 0.84-0.91 (m, 12H).

Example 215 Synthesis of(E)-3-(4-{4-[3-(butyloxycyclohexylmethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylic acid(B967)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 1H), 7.98-8.03 (m, 1H), 7.63(d, 1H, J=2.3 Hz), 7.32-7.40 (m, 3H), 4.40 (d, 1H, J=7.0 Hz), 3.18-3.23(m, 2H), 1.93-1.97 (m, 1H), 1.04-1.64 (m, 14H), 0.86 (t, 3H, J=7.5 Hz).

Example 216 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxy-5-methylhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1053)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 9.29 (s, 1H), 7.89-7.92 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.24-7.37 (m, 3H), 4.53-4.57 (m, 1H), 3.61 (s,3H), 3.16 (s, 3H), 0.87-1.72 (m, 16H).

Example 217 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxy-3,3-dimethylbutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1054)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.89 (dd, 1H, J=1.6, 7.5Hz), 7.71 (s, 1H), 7.40 (d, 1H, J=1.5 Hz), 7.34 (dd, 1H, J=2.1, 7.8 Hz),7.25 (t, 1H, J=7.8 Hz), 4.69 (d, 1H, J=7.5 Hz), 3.63 (s, 3H), 3.13 (s,3H), 1.63-1.71 (m, 4H), 1.36-1.44 (m, 1H), 1.00 (s, 9H).

Example 218 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1059)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.92 (dd, 1H, J=2.4, 7.2Hz), 7.72 (s, 1H), 7.41 (d, 1H, J=1.2 Hz), 7.24-7.38 (m, 2H), 4.55-4.59(m, 1H), 3.62 (s, 3H), 3.15 (s, 3H), 1.50-1.78 (m, 4H), 1.18-1.50 (m,15H), 0.82-0.87 (m, 3H).

Example 219 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxy-undecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1060)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.92 (dd, 1H, J=2.4, 7.5Hz), 7.72 (s, 1H), 7.41 (d, 1H, J=1.5 Hz), 7.24-7.33 (m, 2H), 4.55-4.59(m, 1H), 3.62 (s, 3H), 3.16 (s, 3H), 1.50-1.78 (m, 4H), 1.18-1.50 (m,17H), 0.82-0.87 (m, 3H).

Example 220 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(cyclohexylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1102)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.89 (dd, 1H, J=2.1, 7.5Hz), 7.70 (s, 1H), 7.41 (d, 1H, J=1.5 Hz), 7.30 (dd, 1H, J=2.1, 7.5 Hz),7.25 (t, 1H, J=7.5 Hz), 4.40 (d, 1H, J=6.9 Hz), 3.59 (s, 3H), 3.17-3.24(m, 2H), 1.88-2.00 (m, 1H), 1.69 (s, 3H), 1.44-1.70 (m, 4H), 1.00-1.38(m, 6H), 0.87 (t, 3H, J=7.2 Hz).

Example 221 Synthesis of(E)-3-(4-{4-[3-(1-butyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1122)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.91 (dd, 1H, J=1.8, 7.8Hz), 7.72 (s, 1H), 7.40 (d, 1H, J=1.2 Hz), 7.37 (dd, 1H, J=1.5, 7.5 Hz),7.27 (t, 1H, J=7.8 Hz), 4.80-4.86 (m, 1H), 3.62 (s, 3H), 1.69 (s, 3H),1.23-1.55 (m, 7H), 0.85 (t, 3H, J=7.2 Hz).

Example 222 Synthesis of(E)-3-(4-{4-[3-(3-butyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1124)

1H-NMR(CDCl₃-d6) 8.32 (s, 2H), 7.65 (s, 1H), 7.49 (d, 1H, J=9.0 Hz),7.46 (s, 1H), 7.24-7.28 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 3.58 (s, 3H),3.49 (t, 2H, J=6.6 Hz), 3.44 (t, 2H, J=6.6 Hz), 2.79 (t, 2H, J=7.8 Hz),1.90-2.05 (m, 2H), 1.86 (bs, 3H), 1.53-1.63 (m, 2H), 1.33-1.46 (m, 2H),0.93 (t, 3H, J=7.5 Hz).

Example 223 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1238)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.25 (s, 2H), 7.99-8.05 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.31-7.39 (m, 2H), 6.73 (s, 1H), 4.55-4.59 (m, 1H),3.62 (s, 3H), 3.18 (s, 3H), 1.61-1.79 (m, 2H), 1.26-1.41 (m, 6H),0.80-0.86 (m, 3H).

Example 224 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1250)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.25 (s, 2H), 8.05 (t, 1H, J=7.6 Hz),7.64 (s, 1H), 7.33-7.35 (m, 2H), 6.73 (s, 1H), 4.56 (t, 1H, J=7.6 Hz),3.61 (s, 3H), 3.17 (s, 3H), 1.70-1.80 (m, 2H), 1.22-1.38 (m, 14H),0.87-0.90 (m, 3H).

Example 225 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1437)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.25 (s, 2H), 7.89-7.94 (m, 1H), 7.72(s, 1H), 7.24-7.34 (m, 2H), 6.73 (s, 1H), 4.55-4.59 (m, 1H), 3.62 (s,6H), 3.15 (s, 3H), 1.18-1.80 (m, 16H), 0.82-0.87 (m, 3H).

Example 226 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxyundecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1438)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.25 (s, 2H), 7.89-7.94 (m, 1H), 7.72(s, 1H), 7.24-7.34 (m, 2H), 6.73 (s, 1H), 4.55-4.59 (m, 1H), 3.62 (s,6H), 3.15 (s, 3H), 1.18-1.80 (m, 18H), 0.82-0.87 (m, 3H).

Example 227 Synthesis of(E)-3-(4-{4-[3-(2-ethyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1728)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.55-3.68 (m, 2H), 3.47 (q, 211, J=7.0 Hz), 3.25 (s, 3H), 1.79 (s, 3H),1.10 (t, 3H, J=7.0 Hz).

Example 228 Synthesis of(Z)-3-(4-{4-[3-(2-ethyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1729)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.92 (s, 1H),7.90 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,1H, J=6.5 Hz), 3.71 (s, 3H), 3.55-3.68 (m, 2H), 3.47 (q, 2H, J=7.0 Hz),3.25 (s, 3H), 1.10 (t, 3H, J=7.0 Hz).

Example 229 Synthesis of(E)-3-(4-{4-[3-(2-butyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1730)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.931 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.55-3.68 (m, 2H), 3.42 (t, 2H, J=7.0 Hz), 3.25 (s, 3H), 1.79 (s, 3H),1.40-1.50 (m, 2H), 1.22-1.34 (m, 2H), 0.80 (t, 3H, J=7.0 Hz).

Example 230 Synthesis of(Z)-3-(4-{4-[3-(2-butyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1731)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.92 (s, 1H),7.90 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,1H, J=6.5 Hz), 3.71 (s, 3H), 3.55-3.68 (m, 2H), 3-42 (t, 2H, J=7.0 Hz),3.25 (s, 3H), 1.40-1.50 (m, 2H), 1.22-1.34 (m, 2H), 0.80 (t, 3H, J=7.0Hz).

Example 231 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[1-methyloxy-2-(3-methylbutyloxy)ethyl]phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1732)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.55-3.68 (m, 2H), 3.42 (t, 2H, J=7.0 Hz), 3.25 (s, 3H), 1.79 (s, 3H),1.50-1.60 (m, 1H), 1.22-1.34 (m, 2H), 0.85 (d, 6H, J=6.0 Hz).

Example 232 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[1-methyloxy-2-(3-methylbutyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1733)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.92 (s, 1H),7.90 (s, 1H), 7.66 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,1H, J=6.5 Hz), 3.68 (s, 3H), 3.55-3.68 (m, 2H), 3.42 (t, 2H, J=7.0 Hz),3.25 (s, 3H), 1.50-1.60 (m, 1H), 1.22-1.34 (m, 2H), 0.85 (d, 6H, J=6.0Hz).

Example 233 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-(2-ethyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-phenyl)-2-methylacrylicacid (B1734)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.55-3.68 (m,2H), 3.47 (q, 2H, J=7.0 Hz), 3.25 (s, 3H), 1.69 (s, 3H), 1.10 (t, 3H,J=7.0 Hz).

Example 234 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-ethyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (31735)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.71 (s, 3H), 3.55-3.68 (m, 2H), 3.47 (q, 2H, J=7.0 Hz), 3.25 (s, 3H),1.10 (t, 3H, J=7.0 Hz).

Example 235 Synthesis of(E)-3-(4-{4-[3-(2-butyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (131736)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.55-3.68 (m,2H), 3.42 (t, 2H, J=7.0 Hz), 3.25 (s, 3H), 1.69 (s, 3H), 1.40-1.50 (m,2H), 1.22-1.34 (m, 2H), 0.80 (t, 3H, J=7.0 Hz).

Example 236 Synthesis of(Z)-3-(4-{4-[3-(2-butyloxy-1-methyloxyethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methyloxyacrylicacid (B1737)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.55-3.68 (m, 2H), 3.61 (s, 3H), 3.42 (t, 2H, J=7.0H), 3.25 (s, 3H),1.40-1.50 (m, 2H), 1.22-1.34 (m, 2H), 0.80 (t, 3H, J=7.0 Hz).

Example 237 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[1-methyloxy-2-(3-methylbutyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1738)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.55-3.68 (m,2H), 3.42 (t, 2H, J=7.0 Hz), 3.25 (s, 3H), 1.79 (s, 3H), 1.50-1.60 (m,1H), 1.22-1.34 (m, 2H), 0.85 (d, 6H, J=6.0 Hz).

Example 238 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[1-methyloxy-2-(3-methylbutyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1739)

1H-NMR(DMSO-d6) 13.02 (s, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.55-3.68 (m, 2H), 3.61 (s, 3H), 3.42 (t, 2H, J=7.0 Hz), 3.25 (s, 3H),1.50-1.60 (m, 1H), 1.22-1.34 (m, 2H), 0.85 (d, 6H, J=6.0 Hz).

Example 239 Synthesis of(E)-3-{2,6-difluoro-4-[6-(3-methyloxy-3-methylbutyl)-4,5-dihydronaphthino[1,2-d]thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1742)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.99 (s, 1H), 7.96 (s, 1H), 7.93 (t, 1H,J=7.5 Hz), 7.62 (d, 1H, J=2.3 Hz), 7.33 (s, 1H), 7.19-7.28 (m, 2H), 3.62(t, 2H, J=6.7 Hz), 2.69 (t, 2H, J=6.7 Hz), 1.79 (s, 3H), 1.70-1.79 (m,2H), 1.58-1.69 (m, 2H), 1.30-1.49 (m, 2H).

Example 240 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-3-methylsufanylpropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1744)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.92-8.08 (m, 3H), 7.67 (d, 1H, J=2.7Hz), 7.30-7.44 (m, 3H), 4.71-4.75 (m, 1H), 3.20 (s, 3H), 2.56 (t, 2H,J=7.5 Hz), 1.76-2.10 (m, 8H).

Example 241 Synthesis of(E)-3-(4-{4-[3-(3-t-butyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl]-2-methylacrylicacid (B1746)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.90-8.00 (m, 3H), 7.64 (d, 1H, J=2.7Hz), 7.20-7.34 (m, 3H), 3.66-3.71 (m, 1H), 2.64-2.77 (m, 2H), 1.81 (s,3H), 1.62-1.70 (m, 2H), 1.07-1.15 (m, 12H).

Example 242 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methyloxyheptyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1747)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.93 (t, 1H,J=7.5 Hz), 7.64 (s, 3H), 7.33 (s, 1H), 7.20-7.30 (m, 2H), 3.25 (s, 3H),3.17-3.22 (m, 1H), 2.65-2.72 (m, 2H), 1.78 (s, 3H), 1.70-1.78 (m, 2H),1.45-1.53 (m, 2H), 1.22-1.38 (m, 4H), 0.87-0.90 (m, 3H).

Example 243 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[3-(2-methyloxyethyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1748)

1H-NMR(DMSO-D6) 13.02 (bs, 1H), 7.96 (s, 1H), 7.93 (s, 1H), 7.93 (t, 1H,J=7.5 Hz), 7.64 (s, 1H), 7.33 (s, 1H), 7.20-7.30 (m, 2H), 3.40-3.50 (m,6H), 3.25 (s, 3H), 2.74 (t, 2H, J=7.4 Hz), 1.80-1.88 (m, 2H), 1.80 (s,3H).

Example 244 Synthesis of(E)-3-{4-[4-(3-{1-[2-(2-ethyloxyethyloxy)ethyloxy]propyl}-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B1749)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.92-8.07 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.31-7.44 (m, 3H), 4.67 (t, 1H J=6.3 Hz), 3.20-3.56 (m, 10H),1.67-1.82 (m, 5H), 1.09 (t, 3H, J=7.2 Hz), 0.89 (t, 3H, J=7.2 Hz).

Example 245 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[3-(tetrahydrofuran-2-ylmethyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1750)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.90-7.95 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.20-7.36 (m, 3H), 3.89-3.97 (m, 1H), 3.69-3.76 (m, 1H), 3.58-3.65(m, 1H), 3.45 (t, 4H, J=6.3 Hz), 2.74 (t, 2H, J=7.5 Hz), 1.70-1.94 (m,8H), 1.50-1.60 (m, 1H).

Example 246 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methyloxyheptyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1751)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.29 (s, 2H), 7.85 (t, 1H, J=7.6 Hz),7.64 (s, 1H), 7.40 (s, 1H), 7.20-7.31 (m, 2H), 3.25 (s, 3H), 3.17-3.22(m, 1H), 2.65-2.72 (m, 2H), 1.70-1.80 (m, 2H), 1.68 (s, 3H), 1.45-1.53(m, 2H), 1.22-1.38 (m, 4H), 0.87-0.90 (m, 3H).

Example 247 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1752)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.28 (s, 2H), 7.94 (t, 1H, J=7.6 Hz),7.64 (s, 1H), 7.40 (s, 1H), 7.20-7.31 (m, 2H), 3.20 (s, 3H), 3.17-3.22(m, 1H), 2.65-2.72 (m, 2H), 1.70-1.80 (m, 2H), 1.68 (s, 3H), 1.45-1.53(m, 2H), 1.22-1.38 (m, 8H), 0.87-0.90 (m, 3H).

Example 248 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[3-(2-methyloxyethyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1753)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.28 (s, 2H), 7.94 (t, 1H, J=7.6 Hz),7.64 (s, 1H), 7.40 (s, 1H), 7.20-7.31 (m, 2H), 3.40-3.50 (m, 6H), 3.25(s, 3H), 2.73 (t, 2H, J=7.4 Hz), 1.80-1.88 (m, 2H), 1.68 (s, 3H).

Example 249 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-{1-[2-(2-ethyloxyethyloxy)ethyloxy]propyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1754)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.02 (dt, 1H, J=1.8, 7.5Hz), 7.64 (d, 1H, J=2.4 Hz), 7.38-7.44 (m, 2H), 7.33 (t, 1H, J=7.5 Hz),4.67 (t, 1H, J=6.0 Hz), 3.39-3.56 (m, 10H), 1.67-1.78 (m, 5H), 1.09 (t,3H, J=7.2 Hz), 0.89 (t, 3H, J=6.9 Hz),

Example 250 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[3-(tetrahydrofuran-2-ylmethyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1755)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=2.1, 7.2Hz), 7.64 (d, 1H, J=2.7 Hz), 7.40 (d, 1H, J=1.2 Hz), 7.20-7.32 (m, 2H),3.89-3.97 (m, 1H), 3.69-3.76 (m, 1H), 3.58-3.65 (m, 1H), 3.45 (t, 2H,J=6.6 Hz), 2.74 (t, 2H, J=7.2 Hz), 1.73-1.941 (m, 4H), 1.69 (d, 3H,J=1.8 Hz), 1.50-1.59 (m, 1H)

Example 251 Synthesis of(E)-3-(4-{4-[3-(3-ethyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B1756)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.90-8.10 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.20-7.38 (m, 3H), 3.20-3.45 (m, 4H), 2-73 (t, 2H, J=7.8 Hz),1.76-1.88 (m, 5H), 1.12 (d, 3H, J=6.9 Hz).

Example 252 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-ethyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1757)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.94 (dt, 1H, J=1.8, 6.9Hz), 7.64 (d, 1H, J=2.7 Hz), 7.20-7.33 (m, 3H), 3.30-3.45 (m, 2H),2.70-2.78 (m, 2H), 1.78-1.85 (m, 2H), 1.69 (d, 3H, J=1.5 Hz), 1.12 (t,3H, J=7.2 Hz).

Example 253 Synthesis of(E)-3-[2,6-dichloro-4-(4-(3-[2-(2-ethyloxyethyloxy)ethyloxymethyl]-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1762)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.05 (dt, 1H, J=1.8, 7.8Hz), 7.40-7.48 (m, 2H), 7.32 (d, 1H, J=7.8 Hz), 4.64 (s, 2H), 3.56-3.66(m, 4H), 3.52-3.55 (m, 2H), 3.39-3.48 (m, 4H), 1.09 (d, 3H, J=7.2 Hz).

Example 254 Synthesis of(E)-3-{4-[4-(3-ethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl]-2-methylacrylicacid (B1763)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.92-8.00 (m, 3H), 7.66 (d, 1H, J=2.7Hz), 7.40-7.47 (m, 1H), 7.28-7.37 (m, 3H), 4.59 (s, 2H), 3.52-3.59 (m,2H), 1.81 (d, 3H, J=1.8 Hz), 1.14-1.20 (m, 3H).

Example 255 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-ethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1764)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (d, 2H, J=1.2 Hz), 8.00-8.10 (m,1H), 7.66 (d, 1H, J=2.4 Hz), 7.38-7.47 (m, 2H), 7.31 (t, 1H, J=7.5 Hz),4.59 (s, 2H), 3.52-3.59 (m, 2H), 1.69 (d, 3H, J=0.9 Hz), 1.14-1.20 (m,3H).

Example 256 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-propyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (31765)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.92-8.08 (m, 3H), 7.66 (d, 1H, J=2.4Hz), 7.40-7.47 (m, 1H), 7.28-7.38 (m, 3H), 4.59 (s, 2H), 3.46 (t, 2H,J=6.6 Hz), 1.81 (s, 3H), 1.51-1.64 (m, 2H), 0.90 (t, 3H, J=7.5 Hz).

Example 257 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-propyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1766)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=2.1, 7.8Hz), 7.65 (d, 1H, J=2.4 Hz), 7.38-7.47 (m, 2H), 7.31 (t, 1H, J=6.6 Hz),4.59 (s, 2H), 3.46 (t, 2H, J=6.6 Hz), 1.69 (d, 3H, J=1.2 Hz), 1.52-1.63(m, 4H), 0.90 (t, 3H, J=7.5 Hz).

Example 258 Synthesis of(E)-3-(4-{4-[3-(4-ethyloxybutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl}-2-methylacrylicacid (B1767)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.92-8.08 (m, 3H), 7.66 (d, 1H, J=2.7Hz), 7.40-7.46 (m, 1H), 7.28-7.36 (m, 3H), 4.59 (s, 2H), 3.51 (t, 211,J=6.0 Hz), 3.25-3.42 (m, 4H), 1.69 (d, 3H, J=1.2 Hz), 1.81 (d, 3H, J=1.8Hz), 1.50-1.65 (m, 4H), 1.09 (t, 3H, J=6.9 Hz).

Example 259 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(4-ethyloxybutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl}-2-methylacrylicacid (B1768)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.05 (dt, 1H, J=1.8, 8.1Hz), 7.66 (d, 1H, J=2.4 Hz), 7.39-7.46 (m, 2H), 7.32 (t, 1H, J=7.8 Hz),4.59 (s, 2H), 3.50 (t, 2H, J=6.3 Hz), 3.25-3.41 (m, 4H), 1.69 (d, 3H,J=1.2 Hz), 1.50-1.62 (m, 4H), 1.08 (t, 3H, J=6.9 Hz).

Example 260 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl}-2-methylacrylicacid (B1769)

1H-NMR(DMSO-D6) 13.02 (bs, 2H), 7.92-8.08 (m, 3H), 7.66 (d, 1H, J=2.4Hz), 7.39-7.46 (m, 1H), 7.29-7.36 (m, 3H), 4.86 (s, 2H), 3.52 (t, 2H,J=6.9 Hz), 1.63-1.81 (d, 3H, J=1.8 Hz), 1.65-1.75 (m, 1H), 1.42-1.49 (m,2H), 0.87 (d, 6H, J=6.3 Hz).

Example 261 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl}-2-methylacrylicacid (B1770)

¹H-NMR(DMSO-D6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.01-8.08 (m, 1H), 7.65(d, 1H, J=2.7 Hz), 7.39-7.46 (m, 2H), 7.31 (t, 1H, J=7.8 Hz), 4.59 (s,2H), 3.52 (t, 2H, J=6.9 Hz), 1.63-1.76 (m, 4H), 1.42-1.49 (m, 2H), 0.87(d, 6H, J=6.6 Hz).

Example 262 Synthesis of(E)-3-(4-{4-[3-(1,4-dimethyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluophenyl}-2-methylacrylicacid (B1771)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.92-8.08 (m, 3H), 7.66 (d, 1H, J=2.7Hz), 7.29-7.40 (m, 3H), 4.55-4.62 (m, 1H), 3.19 (s, 6H), 1.48-1.90 (m,7H).

Example 263 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(1,4-dimethyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl}-2-methylacrylicacid (B1772)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.97-8.06 (m, 1H), 7.65(d, 1H, J=2.7 Hz), 7.32-7.42 (m, 3H), 4.50-4.62 (m, 1H), 3.19 (s, 6H),1.40-1.85 (m, 7H).

Example 264 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{3-[3-(2-ethyloxybutyloxy)propyl]-2-fluoro]phenyl}thiazol-2-ylcarbamoyl}phenyl}-2-methyloxyacrylicacid (B1773)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.28 (s, 2H), 7.95 (t, 1H, J=7.6 Hz),7.61 (s, 1H), 7.25-7.35 (m, 2H), 6.73 (s, 1H), 3.61 (s, 3H), 3.39 (s,3H), 3.25 (t, 2H, J=6.0 Hz), 2.74 (t, 2H, J=7.4 Hz), 1.80-1.90 (m, 2H),1.22-1.38 (m, 5H), 0.87 (t, 6H, J=7.4 Hz).

Example 265 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[3-(2,2,2-trifluoroethyloxy)propyl]phenyl]thiazol-2-ylcarbamoyl}phenyl}-2-methylacrylicacid (B1774)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.91-8.00 (m, 3H), 7.64 (d, 1H, J=2.4Hz), 7.22-7.35 (m, 3H), 4.01-4.11 (m, 2H), 3.64 (t, 2H, J=6.0 Hz), 2.75(t, 2H, J=7.5 Hz), 1.84-1.93 (m, 2H), 1.69 (d, 3H, J=1.5 Hz).

Example 266 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[3-(2,2,2-trifluoroethyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1775)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 7.95 (dt, 1H, J=2.1, 7.2Hz), 7.64 (d, 1H, J=2.4 Hz), 7.41 (d, 1H, J=1.5 Hz), 7.22-7.33 (m, 2H),4.01-4.11 (m, 2H), 3.64 (t, 2H, J=6.3 Hz), 2.75 (t, 2H, J=7.5 Hz),1.84-1.93 (m, 2H), 1.81 (d, 3H, J=1.5 Hz).

Example 267 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[3-(3-methyloxybutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1776)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.91-8.02 (m, 3H), 7.67 (d, 1H, J=2.7Hz), 7.20-7.37 (ra, 3H), 3.24-3.45 (m, 5H), 3.20 (s, 3H), 2.70-2.78 (m,2H), 1.77-1.88 (m, 5H), 1.55-1.75 (m, 2H), 1.08 (d, 3H, J=6.3 Hz).

Example 268 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[3-(3-methyloxybutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1777)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.90-8.08 (m, 1H), 7.63(d, 1H, J=2.7 Hz), 7.41 (s, 1H), 7.21-7.32 (m, 2H), 3.36-3.45 (m, 5H),3.20 (s, 3H), 2.71-2.77 (m, 2H), 1.78-1.88 (m, 2H), 1.55-1.75 (m, 5H),1.08 (d, 3H, J=6.3 Hz).

Example 269 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[3-(3-methyloxybutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1778)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.25 (s, 2H), 7.94 (dt, 1H, J=1.5, 6.6Hz), 7.62 (d, 1H, J=2.7 Hz), 7.21-7.32 (m, 2H), 6.73 (s, 1H), 3.61 (s,3H), 3.37-3.44 (m, 5H), 3.20 (s, 3H), 1.76-1.84 (m, 2H), 1.52-1.75 (m,2H), 1.08 (d, 3H, J=6.0 Hz).

Example 270 Synthesis of(E)-3-(4-{4-[3-(ethyloxyphenylmethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl}-2-methylacrylicacid (B1779)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.02 (m, 3H), 7.62 (d, 1H, J=2.6Hz), 7.49-7.53 (m, 1H), 7.25-7.41 (m, 7H), 5.78 (s, 1H), 3.51 (q, 2H,J=7.0 Hz), 1.83 (s, 3H), 1.20 (t, 3H, J=7.0 Hz).

Example 271 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(ethyloxyphenylmethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1780)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.30 (s, 2H), 7.98-8.02 (m, 1H), 7.61(d, 1H, J=2.6 Hz), 7.49-7.53 (m, 1H), 7.25-7.41 (m, 7H), 5.78 (s, 1H),3.51 (q, 2H, J=7.0 Hz), 1.66 (s, 3H), 1.20 (t, 3H, J=7.0 Hz).

Example 272 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-3-phenylpropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1781)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.94-8.06 (m, 3H), 7.65 (d, 1H, J=2.6Hz), 7.15-7.44 (m, 8H), 4.54-4.58 (m, 1H), 3.20 (s, 3H), 2.61-2.73 (m,2H), 1.94-2.09 (m, 2H), 1.81 (s, 3H).

Example 273 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-3-phenylpropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1782)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.30 (s, 2H), 8.00-8.06 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.16-7.44 (m, 8H), 4.54-4.58 (m, 1H), 3.21 (s, 3H),2.64-2.74 (m, 2H), 1.96-2.08 (m, 2H), 1.69 (s, 3H).

Example 274 Synthesis of(E)-3-(4-{4-[3-(2-ethyl-1-methoxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1783)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-8.05 (m, 3H), 7.65 (d, 1H, J=2.6Hz), 7.33-7.36 (m, 3H), 4.51 (d, 1H, 6.4 Hz), 3.16 (s, 3H), 1.81 (d, 3H,J=1.4 Hz), 1.35-1.60 (m, 3H), 1.24-1.36 (m, 2H), 0.81-0.86 (m, 6H).

Example 275 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-ethyloxy-1-methyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1784)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 7.99-8.05 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.4 (s, 1H), 7.34-7.36 (m, 2H), 4.521 (d, 1H, 6.1Hz), 3.16 (s, 3H), 1.39 (s, 3H), 1.38-1.60 (m, 3H), 1.18-1.38 (m, 2H),0.81-0.86 (m, 6H).

Example 275 Synthesis of(E)-3-(4-{4-[3-(3-butyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1785)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 94-8.06 (m, 3H), 7.66 (d, 1H, J=2.5 Hz),7.32-7.42 (m, 3H), 4.68-4.70 (m, 1H), 3.47-3.55 (m, 1H), 3.30-3.38 (m,3H), 1.85-2.01 (m, 2H), 1.81 (s, 3H), 1.42-1.50 (m, 2H), 1.27-1.37 (m,2H), 0.84-0.89 (m, 3H).

Example 277 Synthesis of(E)-3-(4-{4-[3-(3-butyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1786)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.00-8.06 (m, 1H), 7.65(d, 1H, J=2.6 Hz), 7.31-7.41 (m, 3H), 4.68-4.73 (m, 1H), 3.47-3.55 (m, 1μl), 3.28-3.39 (m, 3H), 1.85-2.01 (m, 2H), 1.69 (s, 3H), 1.43-1.50 (m,2H), 1.29-1.34 (m, 2H), 0.84-0.89 (m, 3H).

Example 278 Synthesis of(E)-3-{4-[4-(4′-t-butyl-2-methyloxybiphenyl-3-yl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1787)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 8.04-8.07 (m, 1H), 7.96-7.98 (m, 2H),7.79 (s, 1H), 7.48-7.55 (m, 4H), 7.27-7.34 (m, 3H), 3.31 (s, 3H), 1.81(s, 3H), 1.34 (s, 9H).

Example 279 Synthesis of(E)-3-{4-[4-(4′-t-butyl-2-methyloxybiphenyl-3-yl)thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1788)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.30 (s, 2H), 8.03-8.06 (m, 1H), 7.79(s, 1H), 7.48-7.55 (m, 4H), 7.40 (s, 1H), 7.27-7.35 (m, 2H), 3.31 (s,3H), 1.69 (s, 3H), 1.34 (s, 9H).

Example 280 Synthesis of(E)-3-{4-[4-(4′-t-butyl-2-fluorobiphenyl-3-yl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1789)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.06-8.11 (m, 1H), 7.95-8.00 (m, 2H),7.69 (d, 1H, J=2.6 Hz), 7.34-7.53 (m, 7H), 1.81 (s, 3H), 1.34 (s, 9H).

Example 281 Synthesis of(E)-3-{4-[4-(4′-t-butyl-2-fluorobiphenyl-3-yl)thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1790)

1H-NMR(DMSO-d6) 13.05 (bs, 2H), 8.30 (s, 2H), 8.06-8.10 (m, 1H), 7.69(d, 1H, J=2.6 Hz), 7.37-7.53 (m, 7H), 1.69 (s, 3H), 1.34 (s, 9H).

Example 282 Synthesis of(E)-3-(4-{4-[3-(4-butyloxy-1-methyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1791)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.06 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.32-7.39 (m, 3H), 4.58-4.62 (m, 1H), 3.20-3.44 (m, 4H), 3.19 (s,3H), 1.22-1.88 (m, 11H), 0.85 (t, 3H, J=7.2 Hz).

Example 283 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-4-propyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1792)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.06 (m, 3H), 7.65 (d, 1H, J=2.7Hz), 7.32-7.40 (m, 3H), 4.58-4.62 (m, 1H), 3.25-3.37 (m, 4H), 3.19 (s,3H), 1.41-1.85 (m, 9H), 0.83 (t, 3H, J=7.2 Hz).

Example 284 Synthesis of(E)-3-(4-{4-[3-(4-ethyloxy-1-methyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1793)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 7.94-8.07 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.32-7.40 (m, 3H), 4.58-4.63 (m, 1H), 3.28-3.40 (m, 4H), 3.19 (s,3H), 1.43-1.83 (m, 7H), 1-08 (t, 3H, J=7.2 Hz).

Example 285 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(4-ethyloxy-1-methyloxybutyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1794)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.00-8.05 (m, 1H), 7.65(d, 1H, J=2.7 Hz), 7.32-7.41 (m, 3H), 4.58-4.31 (m, 1H), 3.26-3.40 (m,4H), 3.19 (s, 3H), 1.40-1.88 (m, 7H), 1.08 (t, 3H, J=7.2 Hz).

Example 286 Synthesis of(E)-3-(4-{4-[3-(3,3-dimethylbut-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1795)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.03-8.08 (m, 1H), 7.95-7.98 (m, 2H),7.72 (d, 1H, J=2.7 Hz), 7.26-7.45 (m, 3H), 1.81 (s, 3H), 1.33 (s, 9H).

Example 287 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbut-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1796)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.30 (s, 2H), 8.02-8.08 (m, 1H), 7.72(d, 1H, J=2.6 Hz), 7.40-7.44 (m, 2H), 7.27-7.32 (m, 1H), 1.69 (s, 3H),1.37 (s, 9H).

Example 288 Synthesis of(E)-3-[2,6-difluoro-4-[4-(2-octyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl)-2-methylacrylicacid (B1797)

1H-NMR(DMSO-d6) 12.91 (bs, 2H), 7.92-8.00 (m, 2H), 7.38-7.51 (m, 3H),7.30-7.37 (m, 211), 7.27 (s, 1H), 4.13 (t, 2H, J=6.6 Hz), 1.80-1.92 (m,5H), 1.20-1.52 (m, 10H), 0.83-0.88 (m, 33H).

Example 289 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-octyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl)-2-methylacrylicacid (B1798)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 8.28 (s, 2H), 7.30-7.50 (m, 5H), 7.27(s, 1H), 4.13 (t, 2H, J=6.6 Hz), 1.80-1.90 (m, 2H), 1.69 (d, 3H, J=1.5Hz), 1.18-1.52 (m, 10H), 0.83-0.88 (m, 3H).

Example 290 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxy-4-propyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1799)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.90-8.10 (m, 3H), 7.73 (s, 1H),7.25-7.34 (m, 3H), 4.59-4.63 (m, 1H), 3.62 (s, 3H), 3.16 (s, 3H), 1.81(s, 3H), 1.42-1.76 (m, 6H), 0.84 (t, 3H, J=7.5 Hz).

Example 291 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxy-4-propyloxybutyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1800)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.86 (dd, 1H, J=1.6, 7.5Hz), 7.70 (s, 1H), 7.41 (d, 1H, J=0.9 Hz), 7.31 (dd, 1H, J=1.8, 7.8 Hz),7.25 (t, 1H, J=7.5 Hz), 4.53-4.58 (m, 1H), 3.67-3.74 (m, 2H), 3.15 (s,3H), 1.69 (s, 3H), 1.20-1.40 (m, 19H), 0.83-0.87 (m, 0.3H).

Example 292 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-pent-1-ynylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1801)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.05 (dt, 1H, J=1.8, 7.8 Hz), 7.92-8.00(m, 2H), 7.71 (d, 1H, J=2.7 Hz), 7.43-7.48 (m, 1H), 7.34 (s, 1H), 7.30(t, 1H, J=7.8 Hz), 1.81 (s, 3H), 1.54-1.166 (m, 2H), 1.03 (d, 3H, J=7.5Hz).

Example 293 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-pent-1-ynylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1802)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.28 (s, 2H), 8.05 (dt, 1H, J=2.1, 7.8Hz), 7.66-1.70 (m, 1H), 7.38-7.48 (m, 2H), 7.30 (t, 1H, J=7.8 Hz), 1.69(s, 3H), 1.57-1.64 (m, 2H), 1.03 (d, 3H, J=7.5 Hz).

Example 294 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-pent-1-ynylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1803)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.02-8.10 (m, 1H), 7.90-8.00 (m, 2H),7.68 (d, 1H, J=3.0 Hz), 7.41-7.48 (m, 1H), 7.35 (s, 1H), 7.30 (t, 1H,J=7.8 Hz), 1.81 (s, 3H), 1.56-1.65 (m, 2H), 1.30-1.48 (m, 4H), 0.91 (t,3H, J=7.2 Hz).

Example 295 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-hert-1-ynylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1804)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.28 (s, 2H), 8.05 (dt, 1H, J=1.8, 7.8Hz), 7.69 (d, 1H, J=2.7 Hz), 7.38-7.48 (m, 2H), 7.30 (t, 1H, J=7.8 Hz),1.69 (s, 3H), 1.54-1.63 (m, 2H), 1.31-1.48 (m, 4H), 0.91 (d, 3H, J=7.2Hz).

Example 296 Synthesis of(E)-3-{4-[4-(3-dec-1-ynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B1805)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.05 (dt, 1H, J=1.8, 7.8 Hz), 7.92-8.00(m, 2H), 7.68 (d, 1H, J=2.7 Hz), 7.42-7.47 (m, 1H), 7.34 (s, 1H), 7.30(t, 1H, J=7.8 Hz), 1.80 (s, 1H), 1.52-1.65 (m, 2H), 1.37-1.50 (m, 2H),1.23-1.34 (m, 8H), 0.84-0.89 (m, 3H).

Example 297 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-dec-1-ynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1806)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.28 (s, 2H), 8.02-8.09 (m, 1H), 7.68(d, 1H, J=2.4 Hz), 7.38-7.47 (m, 2H), 7.29 (t, 1H, J=7.8 Hz), 1.69 (s,3H), 1.20-1.62 (m, 12H), 0.82-0.90 (m, 3H).

Example 296 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methylpent-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1807)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.05 (dt, 1H, J=2.1, 7.8 Hz), 7.92-8.00(m, 2H), 7.70 (d, 1H, J=2.7 Hz), 7.42-7.49 (m, 1H), 7.34 (s, 1H), 7.30(t, 1H, J=7.5 Hz), 2.41 (d, 2H, J=6.3 Hz), 1.86-1.94 (m, 1H), 1.80 (s,3H), 1.04 (d, 6H, J=6.9 Hz).

Example 299 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(4-methylpent-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1808)

1H-NMR(DMSO-d6) 13.04 (bs, 2H), 8.29 (s, 2H), 8.05 (dt, 1H, J=1.5, 7.8Hz), 7.70 (d, 1H, J=2.7 Hz), 7.38-7.59 (m, 2H), 7.30 (t, 1H, J=7.8 Hz),2.42 (d, 2H, J=6.3 Hz), 1.83-1.96 (m, 1H), 1.69 (s, 3H), 1.04 (d, 6H,J=6.6 Hz).

Example 300 Synthesis of(E)-3-{4-[4-(3-cyclohexyl-1-enylethynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl)-2-methylacrylicacid (B1809)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.04-8.12 (m, 1H), 7.92-8.02 (m, 2H),7.72 (d, 1H, J=3.0 Hz), 7.44-7.51 (m, 1H), 7.27-7.35 (m, 2H), 6.26-6.30(m, 1H), 2.10-2.24 (m, 4H), 1.81 (s, 3H), 1.46-1.69 (m, 4H).

Example 301 Synthesis of(E)-3-{4-[4-(3-cyclohexy-1-enylethynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl)-2-nmethyloxyacrylicacid (B1810)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.12 (dt, 1H, J=1.8, 7.8 Hz), 7.92-8.00(m, 2H), 7.72 (d, 1H, J=2.4 Hz), 7.51-7.57 (m, 1H), 7.33-7.38 (m, 2H),4.41 (s, 2H), 3.71 (s, 3H), 1.81 (s, 1H).

Example 302 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-propyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1811)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.13 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.72 (s, 1H), 7.52 (t, 1H, J=7.5 Hz), 7.40 (s, 1H), 7.38(t, 1H, J=7.5 Hz), 4.43 (s, 2H), 3.50 (t, 2H, J=7.0 Hz), 1.80 (s, 3H),1.50-1.6 (m, 2H), 0.93 (t, 3H, J=7.0 Hz).

Example 303 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-isopropyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid (B1812)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.11 (t, 1H, J=7.5 Hz), 7.99 (s, 1H),7.96 (s, 1H), 7.72 (s, 1H), 7.52 (t, 1H, J=7.5 Hz), 7.34 (s, 1H), 7.32(t, 1H, J=7.5 Hz), 4.43 (s, 2H), 3.70-3.75 (m, 1H), 1.80 (s, 3H), 1.13(d, 6H, J=6.0 Hz).

Example 304 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-pentyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1813)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.10 (t, 1H, J=7.5 Hz), 7.99 (s, 1H),7.96 (s, 1H), 7.72 (s, 1H), 7.52 (t, 1H, J=7.5 Hz), 7.34 (s, 1H), 7.32(t, 1H, J=7.5 Hz), 4.40 (s, 2H), 3.50 (t, 2H, J=7.0 Hz), 1.80 (s, 3H),1.50-1.61 (m, 2H), 1.20-1.31 (m, 4H), 0.88-0.92 (m, 3H).

Example 305 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-propyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid (B1814)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.28 (s, 2H), 8.10 (t, 1H, J=7.5 Hz),7.72 (s, 1H), 7.52 (t, 1H, J=7.5 Hz), 7.40 (s, 1H), 7.34 (t, 1H, J=7.5Hz), 4.40 (s, 2H), 3.48 (t, 2H, J=7.0 Hz), 1.69 (s, 3H), 1.50-1.61 (m,2H), 0.93 (t, 3H, J=7.0 Hz).

Example 306 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isopropyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1185)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.28 (s, 2H), 8.10 (t, 1H, J=7.5 Hz),7.72 (s, 1H), 7.52 (t, 1H, J=7.5 Hz), 7.40 (s, 1H), 7.34 (t, 1H, J=7.5Hz), 4.40 (s, 2H), 3.70-3.75 (m, 1H), 1.69 (s, 3H), 1.13 (d, 6H, J=6.0Hz).

Example 307 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-pentyloxyprop-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1816)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.28 (s, 2H), 8.10 (t, 1H, J=7.5 Hz),7.72 (s, 1H), 7.44 (t, 1H, J=7.5 Hz), 7.40 (s, 1H), 7.34 (t, 1H, J=7.5Hz), 4.44 (s, 21), 3.51 (t, 2H, J=7.0 Hz), 1.69 (s, 3H), 1.50-1.61 (m,2H), 1.20-1.31 (m, 4H), 0.93 (t, 3H, J=7.0 Hz).

Example 308 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)prop-1-ynyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1817)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.28 (s, 2H), 8.10 (t, 1H, J=7.5 Hz),7.71 (s, 1H), 7.50 (t, 1H, J=7.5 Hz), 7.40 (s, 1H), 7.34 (t, 1H, J=7.5Hz), 4.46 (s, 2H), 3.23 (s, 2H), 1.69 (s, 3H), 0.91 (s, 9H).

Example 309 Synthesis of(E)-3-(4-{4-[3-(5-chloro-pent-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1818)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.07 (t, 1H, J=7.5 Hz), 7.92-8.00 (m,2H), 7.71 (d, 1H, J=3.0 Hz), 7.49 (t, 1H, J=7.2 Hz), 7.29-7.34 (m, 2H),3.81 (t, 2H, J=6.6 Hz), 2.67 (t, 2H, J=7.2 Hz), 1.99-2.08 (m, 2H), 1.81(s, 3H).

Example 310 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(5-chloro-pent-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1819)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.28 (s, 2H), 8.06 (t, 1H, J=6.9 Hz),7.70 (d, 1H, J=2.4 Hz), 7.48 (t, 1H, J=6.3 Hz), 7.40 (s, 1H), 7.31 (t,1H, J=7.8 Hz), 3.81 (t, 2H, J=6.3 Hz), 2.67 (t, 2H, J=6.3 Hz), 1.99-2.08(m, 2H), 1.69 (s, 3H).

Example 311 Synthesis of(E)-3-(4-{4-[3-(5-cyano-pent-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1820)

1H-NMR(DMSO-d6) 8.07 (dt, 1H, J=1.5, 7.8 Hz), 7.91-8.00 (m, 2H), 7.70(d, 1H, J=2.7 Hz), 7.50 (dt, 1H, J=1.5, 6.8 Hz), 7.29-7.34 (m, 2H),2.61-2.69 (m, 4H), 1.85-1.94 (m, 2H), 1.81 (s, 3H).

Example 312 Synthesis of(Z)-3-{4-[4-(3-dec-1-ynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1821)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.04 (dt, 1H, J=1.8, 7.8 Hz), 7.88-7.95(m, 2H), 7.69 (d, 1H, J=2.7 Hz), 7.44 (dt, 1H, J=1.8, 6.6 Hz), 7.29 (t,1H, J=7.8 Hz), 6.64 (s, 1H), 3.71 (s, 3H), 1.16-1.64 (m, 14H), 0.84-0.88(m, 3H).

Example 313 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-pyridin-3-ylethynylphenyl)thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1822)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.81 (s, 1H), 8.64 (d, 1H, J=3.9 Hz),8.17 (t, 1H, J=7.2 Hz), 8.04 (d, 1H, J=7.8 Hz), 7.92-8.10 (m, 2H), 7.77(d, 1H, J=2.1 Hz), 7.67 (t, 1H, J=6.6 Hz), 7.49-7.53 (m, 1H), 7.42 (t,1H, J=7.2 Hz), 7.34 (s, 1H), 1.81 (s, 3H).

Example 314 Synthesis of(E)-3-{4-[4-(3-ethynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1823)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.12 (dt, 1H, J=1.8, 7.5 Hz), 7.92-8.00(m, 2H), 7.72 (d, 1H, J=2.7 Hz), 7.55 (dt, 1H, J=1.5, 6.9 Hz), 7.32-7.37(m, 2H), 4.57 (s, 1H), 1.81 (s, 1H).

Example 315 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methylpent-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1824)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.04 (dt, 1H, J=1.5, 7.5 Hz), 7.87-7.95(m, 2H), 7.71 (d, 1H, J=2.7 Hz), 7.46 (dt, 1H, J=1.8, 7.0 Hz), 7.29 (t,1H, J=7.8 Hz), 6.65 (s, 1H), 3.71 (s, 3H), 2.41 (d, 2H, J=6.6 Hz),1.85-1.94 (m, 1H), 1.04 (d, 6H, J=6.6 Hz).

Example 316 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methylhexan-1-ynyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1825)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.04 (dt, 1H, J=1.8, 7.5 Hz), 7.92-8.00(m, 2H), 7.71 (d, 1H, J=2.7 Hz), 7.43 (dt, 1H, J=1.8, 7.0 Hz), 7.34 (s,1H), 7.29 (t, 1H, J=7.8 Hz), 2.68-2.82 (m, 1H), 1.81 (s, 1H), 1.42-1.64(m, 4H), 1.24 (d, 3H, J=6.9 Hz), 0.91-0.96 (m, 3H).

Example 317 Synthesis of(E)-3-(4-{4-[3-(3-cyclopentylprop-1-ynyl)-2-fluorophenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1826)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.04 (dt, 1H, J=1.8, 6.9 Hz), 7.92-8.00(m, 2H), 7.70 (d, 1H, J=2.7 Hz), 7.44 (dt, 1H, J=1.8, 7.0 Hz), 7.33 (s,1H), 7.30 (t, 1H, J=7.8 Hz), 2.05-2.17 (m, 1H), 1.76-1.87 (m, 5H),1.48-1.70 (m, 4H), 1.29-1.40 (m, 2H).

Example 318 Synthesis of(Z)-3-{4-[4-(3-cyclohexy-1-enylethynyl-2-fluorophenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1827)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.07 (dt, 1H, J=1.5, 7.5 Hz), 7.87-7.95(m, 2H), 7.72 (d, 1H, J=2-7 Hz), 7.48 (dt, 1H, J=1.8, 6.0 Hz), 7.32 (t,1H, J=7.8 Hz), 6.65 (s, 1H), 6.25-6.30 (m, 1H), 3.71 (s, 3H), 2.10-2.24(m, 4H), 1.54-1.70 (m, 4H).

Example 319 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyl)-2-fluorophenyl]-5-morpholin-4-ylthiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1828)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.23 (s, 2H), 7.42 (t, 1H, J=7.6 Hz),7.40 (s, 1H), 7.29 (t, 1H, J=7.6 Hz), 7.09 (d, 1H, J=7.6 Hz), 3.66-3.72(m, 4H), 2.166-2.78 (m, 4H), 2.60-2.70 (m, 2H), 1.68 (s, 3H), 1.39-1.45(m, 2H), 0.95 (s, 9H).

Example 320 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-morpholin-4-ylthiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1829)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.92 (s, 1H), 7.89 (s, 1H), 7.50 (t, 1H,J=7.5 Hz), 7.39 (t, 1H, J=7.5 Hz), 7.33 (s, 1H), 7.28 (t, 1H, J=7.5 Hz),4.51 (t, 1H, J=6.5 Hz), 3.66-3.72 (m, 4H), 3.16 (s, 3H), 2.75-2.86 (m,4H), 1.78 (s, 3H), 1.70-1.78 (m, 2H,), 1.12-1.38 (m, 6H), 0.87-0.90 (m,3H).

Example 321 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-morpholin-4-ylthiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1830)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.23 (s, 2H), 7.50 (t, 1H, J=7.6 Hz),7.38 (s, 1H), 7.36 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz), 4.51 (t,1H, J=6.5H, z), 3.66-3.72 (m, 4H), 3.16 (s, 3H), 2.75-2.86 (m, 4H),1.70-1.78 (m, 2H,), 1.68 (s, 3H), 1.10-1.38 (m, 6H), 0.87-0.90 (m, 3H).

Example 322 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-propyloxypropyl)phenyl]-5-morpholin-4-ylthiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1831)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 742 (t, 1H, J=7.6 Hz),7.38 (s, 1H), 7.28 (t, 1H, J=7.6 Hz), 7.17 (t, 1H, J=7.6 Hz), 3.75-3.89(m, 4H), 3.33-3.40 (m, 4H), 2.75-2.86 (m, 4×), 2.74 (t, 1H, J=7.0 Hz),1.70-1.78 (m, 2H), 1.68 (s, 3H), 1.20-1.30 (m, 2H), 0.87 (t, 3H, J=7.0Hz).

Example 323 Synthesis of(E)-3-(4-{4-[3-(3-dimethylamino-prop-1-ynyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1832)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.08 (dt, 1H, J=1.8, 7.5H), 7.72 (d, 1H,J=2.4 Hz), 7.51 (dt, 1H, J=1.8, 7.2H), 7.30-7.54 (m, 2H), 3.56 (s, 2H),2.29 (s, 6H), 1.81 (s, 3H).

Example 324 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1833)

1H-NMR(CDCl₃-d6) 8.31 (s, 2H), 7.66 (s, 1H), 7.46-7.53 (m, 2H),7.24-7.30 (m, 1H), 7.17 (t, 1H J=7.8 Hz), 3.59 (s, 3H), 3.46-3.52 (m,2H), 3.08 (s, 2H), 2.76-2.84 (m, 2H), 1.92-1.98 (m, 2H), 1.87 (s, 3H),0.94 (s, 9H).

Example 325 Synthesis of(E)-3-(4-{4-[3-(2-butyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1834)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.98 (m, 2H), 7.86-7.88 (m, 1H),7.73 (s, 1H), 7.34 (s, 1H), 7.27-7.29 (m, 1H), 7.14-7.19 (m, 1H),3.59-3.65 (m, 5H), 3.40 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.81(s, 3H), 1.42-1.50 (m, 2H), 1.26-1.34 (m, 2H), 0.86 (t, 3H, J=7.0 Hz).

Example 326 Synthesis of(Z)-3-(4-{4-[3-(2-butyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1835)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.85-7.93 (m, 3H), 7.72 (s, 1H),7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.66 (s, 1H), 3.71 (s, 3H),3.59-3.65 (m, 5H), 3.41 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz),1.43-1.50 (m, 2H), 1.27-1.34 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 327 Synthesis of(E)-3-(4-{4-[3-(2-butyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1836)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 8.26 (s, 2H), 7.85-7.89 (m, 1H), 7.72(s, 1H), 7.40 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H), 3.59-3.65(m, 5H), 3.41 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.69 (s, 3H),1.43-1.50 (m, 2H), 1.27-1.34 (m, 2H), 0.86 (t, 3H, J=7.0 Hz).

Example 328 Synthesis of(Z)-3-(4-{4-[3-(2-butyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methyloxyacrylicacid (B1837)

1H-NMR(DMSO-d6) 12.94 (bs, 2H), 8.24 (s, 2H), 7.85-7.87 (m, 1H), 7.71(s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.73 (s, 1H), 3.59-3.65(m, 5H), 3.41 (t, 2H, J=6.6 Hz), 3.20 (s, 3H), 2.91 (t, 2H, J=6.9 Hz),1.43-1.50 (m, 2H), 1.27-1.34 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 329 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(2-propyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1838)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.97 (m, 2H), 7.85-7.89 (m, 1H),7.72 (s, 1H), 7.34 (s, 1H), 7.26-7.29 (m, 1H), 7.14-7.19 (m, 1H),3.60-3.65 (m, 5H), 3.70 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6-9 Hz), 1.81(s, 3H), 1.45-1.52 (m, 2H), 0.85 (t, 3H, J=7.5 Hz).

Example 330 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(2-propyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1839)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.85-7.88 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.27-7.30 (m, 1H), 7.14-7.19 (m, 1H), 3.60-3.66(m, 5H), 3.37 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=7.0 Hz), 1.69 (s, 3H),1.48-1.54 (m, 2H), 0.85 (t, 3H, J=7.5 Hz).

Example 331 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2]methyloxy-3-(2-propyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1840)

1H-NMR(DMSO-d6) 13.52 (bs, 1H), 12.98 (bs, 1H), 8.25 (s, 2H), 7.85-7.88(m, 1H), 7.72 (s 1H), 7.26-7.30 (m, 1H), 7.14-7.19 (m, 1H), 6.74 (s,1H), 3.60-3.66 (m, 8H), 3.70 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=7.0 Hz),1.48-1.54 (m, 2H), 0.85 (t, 3H, J=7.5 Hz).

Example 332 Synthesis of(E)-3-{4-[4-(3-butyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B1841)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.95-7.98 (m, 2H), 7.60-7.65 (m, 2H),7.40 (s, 1H), 7.14-7.24 (m, 2H), 4.09 (t, 2H, J=6.6 Hz), 1.80 (s, 3H),1.70-1.77 (m, 2H), 1.43-1.51 (m, 2H), 0.97 (t, 3H, J=7.5 Hz)

Example 333 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxybutyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1842)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.50 (t, 1H,J=7.5 Hz), 7.28-7.38 (m, 3H), 4.53 (t, 1H, J=6.5 Hz), 3.95 (s, 3H), 3.17(s, 3H), 1.79 (s, 3H), 1.50-1.78 (m, 2H,), 1.20-1.30 (m, 2H), 0.87 (t,3H, J=7.0 Hz).

Example 334 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxybutyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B11843)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 746 (t, 1H, J=7.6 Hz),7.38 (s, 1H), 7.34 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz), 4.58 (t,1H, J=6.5 Hz), 3.95 (s, 3H), 3.17 (s, 3H), 1.69 (s, 3H), 1.50-1.78 (m,2H), 1.20-1.30 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 335 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isopropyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B18.43)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.72 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.61 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 2H), 3.17 (s, 3H),1.80-1.99 (m, 2H), 1.05 (d, 6H, J=6.0 Hz).

Example 336 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxybutyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1845)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.25 (s, 2H), 746 (t, 1H, J=7.6 Hz),7.34 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz), 6.72 (s, 1H), 4.53 (t,1H, J=6.5 Hz), 3.9 (s, 3H), 3.60 (s, 3H), 3.17 (s, 3H), 1.50-1.7 (m,2H), 1.20-1.30 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 337 Synthesis of(E)-3-(4-{4-[3-(3,3-dimethylbutyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1846)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.97 (s, 1H), 7.96 (s, 1H), 7.77 (s,1H), 7.75 (t, 1H, J=7.5), 7.38 (s, 1H), 7.12 (t, 1H, J=7.5), 3.99 (s,3H), 2.50-2.60 (m, 2H), 1.78 (s, 3H), 1.39-1.45 (m, 2H), 0.95 (s, 9H).

Example 338 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1847)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 7.77 (s, 1H), 7.74 (t, 1H,J=7.6 Hz), 7.41 (s, 1H), 7.32 (t, 1H, J=7.6 Hz), 4.05 (s, 3H), 2.50-2.60(m, 2H), 1.68 (s, 3H), 1.39-1.45 (m, 2H), 0.95 (s, 9H).

Example 339 Synthesis of(E)-3-[4-(4-{3-[3-(2-ethylbutyloxy)propyl]-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B1848)

1H-NMR(CDCl3-D6) 7.90 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.45-7.50 (m,2H), 7.25-7.28 (m, 1H), 7.17 (t, 1H, J=7.2 Hz), 3.57 (s, 3H), 3.49 (t,2H, J=6.0 Hz), 3.33 (d, 2H, J=5.4 Hz), 2.76-2.84 (m, 2H), 1.90-2.11 (m,5H), 1.30-1.50 (m, 5H), 0.90 (t, 6H, J=7.2 Hz).

Example 340 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[3-(2-ethylbutyloxy)propyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1849)

1H-NMR(CDCl₃-d6) 8.33 (s, 2H), 7.65 (s, 1H), 7.46-7.52 (m, 2H),2.25-7.28 (m, 1H), 7.17 (t, 1H, J=7.8 Hz), 3.58 (s, 3H), 3.47 (t, 2H,J=6 Hz), 3.32 (d, 2H, J=5.7 Hz), 2.76-2.82 (m, 2H), 1.90-2.00 (m, 2H),1.86 (bs, 3H), 1.31-1.50 (m, 5H), 0.89 (t, 6H, J=7.5 Hz).

Example 341 Synthesis of(Z)-3-[4-(4-{3-[3-(2-ethylbutyloxy)propyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methyloxyacrylicacid (B1850)

1H-NMR(CDCl₃-d6) 7.82 (s, 1H), 7.79 (s, 1H), 7.40-7.50 (m, 2H),7.25-7.26 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 6.92 (s, 1H), 3.90 (s, 3H),3.48 (t, 2H, J=6.3 Hz), 3.32 (d, 2H, J=5.7 Hz), 2.76-2.83 (m, 2E),1.91-2.05 (m, 2H), 1.31-1.52 (m, 5H), 0.90 (t, 6H, J=7.5 Hz).

Example 342 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[3-(3-methylbutyloxy)propyl]phenylthiazol-2-ylcarbamoyl)phenyl}-2-methylacrylicacid (B1851)

1H-NMR(CDCl3-D6) 7.91 (s, 1H), 7.88 (s, 1H), 7.57 (bs, 1H), 7.47-7.52(m, 1H), 7.47 (s, 1H), 7.25-7.30 (m, 1H), 7.18 (t, 1H, J=7.5 Hz), 3.58(s, 3H), 3.44-3.52 (m, 4H), 2.80 (t, 2H, J=8.7 Hz), 1.91-2.00 (m, 5H),1.68-1.78 (M, 1H), 1.49 (q, 2H, J=13.8, 6.9 Hz), 0.92 (d, 6H, J=6.3 Hz).

Example 343 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-methyloxy-3-[3-(3-methylbutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1852)

¹H-NMR(CDCl3-D6) 8.31 (s, 2H), 7.65 (s, 1H), 7.50 (Dd, 1H, J=7.8, 1.5Hz), 7.46 (s, 1H), 7.24-7.28 (m, 1H), 7.16 (t, 1H, J=7.8 Hz), 3.58 (s,3H), 3.43-3.51 (m, 4H), 2.76-2.82 (m, 2H), 1.85-2.05 (m, 2H), 1.86 (s,3H), 1.65-1.80 (m, 1H), 1.49 (t, 2H, J=13.5, 6.6 Hz), 0.92 (d, 6H, J=6.9Hz).

Example 344 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[3-(3-methylbutyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1853)

1H-NMR(CDCl₃-D6) 7.84 (s, 1H), 7.81 (s, 1H), 7.49 (d, 1H, J=8.1 Hz),7.46 (s, 1H), 7.29 (d, 1H, J=7.5 Hz), 7.18 (t, 1H, J=7.5 Hz), 6.91 (s,1H), 3.90 (s, 3H), 3.59 (s, 3H), 2.40-3.52 (m, 4H), 2.80 (t, 2H, J=8.1Hz), 1.90-2.05 (m, 2H), 1.65-1.78 (m, 1H), 1.49 (q, 2H, J=13.5, 6.6 Hz),0.92 (d, 6H, J=6.3 Hz).

Example 345 Synthesis of(E)-3-(4-{4-[3-(3-cyclobutylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1854)

1H-NMR(CDCl₃-d6) 7.91 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.49 (dd, 1H,J=7.5, 1.5 Hz), 7.46 (s, 1H), 7.25-7.29 (m, 1H), 7.18 (t, 1H, J=7.5 Hz),3.58 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 3.43 (d, 2H, J=6.9 Hz), 2.76-2.82(m, 2H), 2.54-2.64 (m, 1H), 1.72-1.21 (m, 11H).

Example 346 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-cyclobutylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1855)

1H-NMR(CDCl₃-d6) 8.32 (s, 2H), 7.66 (s, 1H), 7.49 (d, 1H, J=6.6 Hz),7.46 (s, 1H), 7.24-7.26 (m, 1H), 7.16 (t, 1H, J=7.5 Hz), 3.57 (s, 3H),3.49 (t, 2H, 6.3 Hz), 3.42 (d, 2H, J=6.6 Hz), 2.78 (t, 2H, J=7.8 Hz),2.52-2.64 (m, 1H), 2.01-2.12 (m, 2H), 1.70-2.00 (m, 9H).

Example 347 Synthesis of(Z)-3-(4-{4-[3-(3-cyclobutylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1856)

1H-NMR(CDCl₃-D6) 7.82 (s, 1H), 7.79 (s, 1H), 7.44-7.50 (m, 2H),7.25-7.30 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 6.92 (s, 1H), 3.91 (s, 3H),3.57 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 3.43 (d, 2H, J=6.9 Hz), 2.79 (t,2H, J=7.8 Hz), 2.53-2.66 (m, 1H), 1.72-2.13 (m, 8H).

Example 348 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3-cyclobutylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1857)

1H-NMR(CDCl₃-d6) 8.25 (s, 2H), 7.47 (d, 1H, J=7.8 Hz), 7.44 (s, 1H),7.24-7.26 (m, 1H), 7.16 (t, 1H, J=7.5 Hz), 7.02 (s, 1H), 3.73 (s, 3H),3.57 (s, 3H), 3.49 (t, 2H, J=6.0 Hz), 3.42 (d, 2H, J=6.6 Hz), 2.78 (t,2H, J=8.1 Hz), 2.53-2.64 (m, 1H), 1.71-2.14 (m, 8H).

Example 349 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-methyoxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (11858)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.48 (t, 1H,J=7.5 Hz), 7.28-7.38 (m, 3H), 4.51 (t, 1H, J=6.5 Hz), 3.95 (s, 3H), 3.17(s, 3H), 1.79 (s, 3H), 1.50-1.78 (m, 2H), 1.20-1.30 (m, 6H), 0.87-0.90(m, 3H).

Example 350 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-methyoxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1859)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 7.46 (t, 1H, J=7.6 Hz),7.38 (s, 1H), 7.34 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz), 4.51 (t,1H, J=6.5 Hz), 3.95 (s, 3H), 3.17 (s, 3H), 1.50-1.78 (m, 2H), 1.69 (s,3H), 1.20-1.30 (m, 6H), 0.87-0.90 (m, 3H).

Example 351 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-methyoxythiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1860)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.48 (t, 1H,J=7.5 Hz), 7.36 (t, 1H, J=7.5 Hz), 7.28 (t, 1H, J=7.5 Hz), 6.65 (s, 1H),4.51 (t, 1H, J=6.5 Hz), 3.95 (s, 3H), 3.70 (s, 3H), 3.17 (s, 3H),1.50-1.78 (m, 2H,), 1.20-1.30 (m, 6H), 0.87-0.90 (m, 3H).

Example 352 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyhexyl)phenyl]-5-methyoxythiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1861)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.20 (s, 2H), 7.46 (t, 1H, J=7.6 Hz),7.34 (t, 1H, J=7.6 Hz), 7.28 (t, 1H, J=7.6 Hz), 6.65 (s, 1H), 4.51 (t,1H, J=6.5 Hz), 3.95 (s, 3H), 3.60 (s, 3H), 3.17 (s, 3H), 1.50-1.78 (m,2H), 1.20-1.30 (m, 6H), 0.87-0.90 (m, 3H).

Example 353 Synthesis of(E)-3-(2,6-difluoro-4-{5-methyloxy-4-[3-(3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1862)

1H-NMR(DMSO-D6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.77 (s,1H), 7.76 (d, 1H, J=7.5 Hz), 7.34 (s, 1H), 7.33 (t, 1H, J=7.6 Hz), 7.11(t, 1H, J=7.6 Hz), 4.05 (s, 3H), 3.33-3.40 (m, 4H), 2.74 (t, 1H, J=7.0Hz), 1.75-1.85 (m, 2H), 1.79 (s, 3H), 1.45-1.55 (m, 2H), 0.87 (t, 3H,J=7.0 Hz).

Example 354 Synthesis of(E)-3-(2,6-dichloro-4-{5-methyloxy-4-[3-(3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1863)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.28 (s, 2H), 7.77 (s, 1H), 7.76 (d, 1H,J=7.5 Hz), 7.39 (s, 1H), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6 Hz),4.05 (s, 3H), 3.33-3.40 (m, 4H), 2.74 (t, 1H, J=7.0 Hz), 1.75-1.85 (m,2H), 1.68 (s, 3H), 1.45-1.55 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 355 Synthesis of(Z)-3-(2,6-difluoro-4-{5-methyloxy-4-[3-(3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1864)

1H-NMR(DMSO-D6) 13.02 (bs, 1H), 7.88 (s, 1H), 7.85 (s, 1H), 7.77 (s,1H), 7.76 (d, 1H, J=7.5 Hz), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6Hz), 6.63 (s, 1H), 4.05 (s, 3H), 3.79 (s, 3H), 3.33-3.40 (m, 4H), 2.74(t, 1H, J=7.0 Hz), 1.75-1.85 (m, 2H), 1.45-1.55 (m, 2H), 0.87 (t, 3H,J=7.0 Hz).

Example 356 Synthesis of(Z)-3-(2,6-dichloro-4-{5-methyloxy-4-[3-(3-propyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1865)

1H-NMR(DMSO-D6) 13.02 (bs, 1H), 8.28 (s, 2H), 7.77 (s, 1H), 7.76 (d, 1H,J=7.5 Hz), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6 Hz), 6.63 (s, 1H),4.05 (s, 3H), 3.70 (s, 3H), 3.33-3.40 (m, 4H), 2.64 (t, 1H, J=7.0 Hz),1.75-1.85 (m, 2H), 1.45-1.55 (m, 2H), 0.87 (t, 3H, J=7.0 Hz).

Example 357 Synthesis of(E)-3-(4-{4-[3-(3-ethyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1866)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.03 (dt, 1H, J=2.4, 7.5 Hz), 7.93-7.99(m, 2H), 7.66 (d, 1H, J=2.7 Hz), 7.32-7.41 (m, 3H), 4.68-4.73 (m, 1H),3.47-3.54 (m, 1H), 3.36-3.43 (m, 2H), 3.18 (s, 3H), 1.85-2.02 (m, 2H),1.81 (s, 3H), 1.09 (t, 3H, J=6.9 Hz).

Example 358 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-ethyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1867)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.27 (s, 2H), 8.01 (dt, 1H, J=3.0, 6.6Hz), 7.63 (d, 1H, J=2.4 Hz), 7.30-7.39 (m, 3H), 4.66-4.71 (m, 1H),3.45-3.53 (m, 1H), 3.16 (s, 3H), 1.83-2.00 (m, 2H), 1.67 (s, 3H), 1.07(t, 3H, J=6.9 Hz).

Example 359 Synthesis of(E)-3-{4-[4-(3-benzyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1868)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 7.95-7.98 (m, 2H), 7.77 (s, 1H),7.66-7.69 (m, 1H), 7.34-7.54 (m, 6H), 7.13-7.15 (m, 2H), 5.20 (s, 2H),3.82 (s, 3H), 1.81 (s, 3H).

Example 360 Synthesis of(Z)-3-{4-[4-(3-benzyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1869)

1H-NMR(DMSO-d6) 12.89 (bs, 2H), 7.89-7.92 (m, 2H), 7.76 (s, 1H),7.66-7.69 (m, 1H), 7.34-7.53 (m, 5H), 7.13-7.15 (m, 2H), 6.66 (s, 1H),5.19 (s, 2H), 3.82 (s, 3H), 3.71 (s, 3H).

Example 361 Synthesis of(E)-3-{4-[4-(3-benzyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methylacrylicacid (B1870)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.29 (s, 2H), 7.76 (s, 1H), 7.66-7.69(m, 1H), 7.35-7.54 (m, 6H), 7.13-7.15 (m, 2H), 5.20 (s, 2H), 3.82 (s,3H), 1.69 (s, 3H).

Example 362 Synthesis of(Z)-3-{4-[4-(3-benzyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl)-2-methyloxyacrylicacid (B1871)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 8.24 (s, 2H), 7.76 (s, 1H), 7.66-7.69(m, 1H), 7.35-7.54 (m, 5H), 7.13-7.15 (m, 2H), 6.74 (s, 2H), 5.20 (s,1H), 3.82 (s, 3H), 3.61 (s, 3H).

Example 363 Synthesis of(E)-3-(4-{4-[3-(4-chlorobutyloxy)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1872)

1H-NMR(DMSO-D6) 12.93 (bs, 2H), 7.95-7.97 (m, 2H), 7.75 (s, 1H),7.64-7.67 (m, 1H), 7.33 (s, 1H), 7.11-7.16 (m, 1H), 7.03-7.06 (m, 1H),4.06-4.10 (m, 2H,), 3.80 (s, 3H), 3.74-3.78 (m, 2H), 1.93 (bs, 4H), 1.81(s, 3H).

Example 364 Synthesis of(E)-3-(4-{4-[3-(4-chlorobutyloxy)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1873)

1H-NMR(DMSO-d6) 12.89 (bs, 2H), 7.89-7.92 (m, 2H), 7.75 (s, 1H),7.65-7.67 (m, 1H), 7.11-7.16 (m, 1H), 7.03-7.06 (m, 1H), 6.67 (s, 1H),4.06-4.10 (m, 2H,), 3.80 (s, 3H), 3.74-3.78 (m, 2H), 3.71 (s, 3H), 1.93(bs, 4H).

Example 365 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(4-chlorobutyloxy)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1874)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 8.29 (s, 2H), 7.75 (s, 1H), 7.65-7.67(m, 1H), 7.40 (s, 1H), 7.11-7.16 (m, 1H), 7.03-7.06 (m, 1H), 4.06-4.10(m, 2H,), 3.80 (s, 3H), 3.74-3.78 (m, 2H), 1.93 (bs, 4H), 1.69 (s, 3H).

Example 366 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(3-methyloxypropylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1875)

1H-NMR(CDCl₃-d6) 7.90 (s, 1H), 7.88 (s, 1H), 7.58 (s, 1H), 7.49 (d, 1H,J=6.3 Hz), 7.46 (s, 1H), 7.25-7.28 (m, 1H), 7.18 (t, 1H, J=7.5 Hz), 3.57(s, 3H), 3.47 (t, 2H, J=6.3 Hz), 3.37 (s, 3H), 2.79 (t, 2H, J=8.1 Hz),1.93-2.00 (m, 5H).

Example 367 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-methyloxypropylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1876)

1H-NMR(CDCl₃-d6) 8.32 (s, 2H), 7.66 (s, 1H), 7.45-7.51 (m, 2H),7.24-7.27 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 3.57 (s, 3H), 3.46 (t, 2H,J=6.3 Hz), 3.37 (s, 3H), 2.78 (t, 2H, J=8.7 Hz), 1.90-2.04 (m, 2H), 1.87(s, 3H).

Example 368 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-(3-isobuyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcabamoyl}phenyl)-2-methylacrylicacid (B1877)

1H-NMR(CDCl3-d6) 7.90 (s, 1H), 7.87 (s, 1H), 7.58 (s, 1H), 7.45-7.52 (m,2H), 7.24-7.30 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 3.57 (s, 3H), 3.50 (t,2H, 6.3 Hz), 3.21 (d, 2H, J=6.6 Hz), 2.80 (t, 2H, 8.7 Hz), 1.84-2.03 (m,6H), 0.93 (d, 6H, J=6.3 Hz).

Example 369 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-isobuyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1878)

1H-NMR(CDCl₃-d6) 8.32 (s, 2H), 7.66 (s, 1H), 7.45 (d, 1H, J=7.2 Hz),7.46 (s, 1H), 7.24-7.28 (m, 1H,), 7.16 (t, 1H, J=7.5 Hz), 3.57 (s, 3H),3.49 (t, 2H, J=6.0 Hz), 3.20 (d, 2H, J=6.6 Hz), 2.80 (t, 2H, J=8.4 Hz),1.83-2.04 (m, 6H), 0.92 (d, 6H, J=6.3 Hz).

Example 370 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[3-(3-isobuyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcabamoyl}phenyl)-2-methyloxyacrylicacid (B1879)

1H-NMR(CDCl₃-d6) 7.80 (s, 1H), 7.78 (s, 1H), 7.46 (dd, 1H, J=7.8, 2.1Hz), 7.44 (s, 1H), 7.25-7.32 (m, 1H), 7.17 (t, 1H, J=7.5 Hz), 6.92 (s,1H), 3.91 (s, 3H), 3.57 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 3.21 (d, 2H,J=6.6 Hz), 2.80 (t, 2H, J=8.7 Hz), 1.83-2.01 (m, 3H), 0.93 (d, 6H, J=6.3Hz).

Example 371 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3-isobuyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1880)

1H-NMR(CDCl₃-d6) 8.25 (s, 2H), 7.47 (dd, 1H, J=7.8, 1.8 Hz), 7.44 (s,1H), 7.24-7.28 (m, 1H), 7.16 (t, 1H, J=7.5 Hz), 7.03 (s, 1H), 3.73 (s,3H), 3.57 (s, 3H), 3.49 (t, 2H, J=6.3 Hz), 3.20 (d, 2H, J=6.9 Hz), 2.79(t, 2H, J=8.4 Hz), 1.83-2.00 (m, 3H), 0.92 (d, 6H, J=6.9 Hz).

Example 372 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(3-propylcoxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1881)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 7.93-7.97 (m, 3H), 7.72 (s, 1H),7.32-7.38 (m, 2H), 7.22 (t, 1H, J=7.5 Hz), 4.55 (s, 2H), 3.64 (s, 3H),3.45 (t, 2H, J=6.6 Hz), 1.79 (d, 3H, J=1.5 Hz), 1.54-1.61 (m, 2H), 0.89(t, 3H, J=7.2 Hz).

Example 373 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-propyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1882)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.27 (s, 2H), 7.94-7.97 (m, 1H), 7.71(s, 1H), 7.36-7.38 (m, 2H), 7.22 (t, 1H, J=7.5 Hz), 4.55 (s, 2H), 3.64(s, 3H), 3.45 (t, 211, J=6.6 Hz), 1.67 (s, 3H), 1.54-1.61 (m, 2H), 0.89(t, 3H, J=7.3 Hz).

Example 374 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-propyloxymethylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1883)

1H-NMR(DMSO-D6) 12.95 (bs, 2H), 8.24 (s, 2H), 7.97 (dd, 1H, J=3.0 Hz,7.65 Hz), 7.73 (s, 1H), 7.37-7.40 (m, 1H), 7.24 (t, 1H, J=7.8 Hz), 6.72(s, 1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.61 (s, 3H), 3.47 (t, 2H, J=6.3Hz), 1.55-1.62 (m, 2H), 0.91 (t, 3H, J=7.2 Hz).

Example 375 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1884)

1H NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.34-7.40 (m, 2H), 7.24 (t, 1H, J=7.8 Hz), 41.6 (s, 2H), 3.65 (s, 3H),3.50 (t, 2H, J=6-6 Hz), 1.81 (d, 3H, J=1.8 Hz), 1.55-1.59 (m, 2H)1.30-1.34 (m, 4H), 0.85-0.90 (m, 3H).

Example 376 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(3-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1885)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H),7.37-7.40 (m, 1H), 7.24 (t, 1H, J=7.5 Hz), 6.67 (s, 1H), 4.56 (s, 2H),3.72 (s, 3H), 3.65 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 1.55-1.60 (m, 2H),1.30-1.34 (m, 4H), 0.87 (t, 3H, J=6.9 Hz).

Example 377 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1886)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.96-7.99 (m, 1H), 7.74(s, 1H), 7.36-7.41 (m, 2H), 7.24 (t, 1H, J=7.8 Hz), 4.56 (s, 2H), 3.65(s, 3H), 3.50 (t, 2H, J=6.3 Hz), 1.69 (d, 3H, J=1.5 Hz), 1.55-1.60 (m,2H), 1.30-1.34 (m, 4H), 0.87 (t, 3H, J=6.9 Hz).

Example 378 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1887)

1H NMR(DMSO-d6) 12.97 (bs, 2H), 8.25 (s, 2H), 7.97 (dd, 1H, J=1.5 Hz,7.8 Hz), 7.74 (s, 1H), 7.37-7.40 (m, 1H), 7.24 (t, 1H, J=7.5 Hz), 6.72(s, 1H), 4.56 (s, 2H), 3.65 (s, 3H), 3.62 (s, 3H), 3.50 (t, 2H, J=6.3Hz), 1.55-1.60 (m, 2H), 1.30-1.34 (m, 4H), 0.87 (t, 3H, J=6.9 Hz).

Example 379 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-isopropyloxy-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1888)

1H NMR(DMSO-d6) 12.96 (bs, 2H), 7.96 (d, 3H, J=8.1 Hz), 7.74 (s, 1H),7.38-7.40 (m, 1H), 7.34 (s, 1H), 7.23 (t, 1H, J=7.5 Hz), 4.56 (s, 2H),3.68-3.76 (m, 1H), 3.66 (s, 3H), 1.81 (s, 3H), 1.19 (d, 6H, J=6.3 Hz).

Example 380 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-isopropyloxy-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1889)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.96 (dd, 1H, J=1.5 Hz,8.1 Hz), 7.74 (s, 1H), 7.37-7.41 (m, 2H), 7.23 (t, 1H, J=7.8 Hz), 4.56(s, 2H), 3.68-3.76 (m, 1H), 3.66 (s, 3H), 1.69 (d, 3H, J=1.5 Hz), 1.19(d, 6H, J=6.3 Hz).

Example 381 Synthesis of(E)-3-(4-{4-[3-(1-ethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1890)

1H NMR(DMSO-d6) 13.20 (bs, 2H), 7.96 (d, 3H, J=8.7 Hz), 7.73 (s, 1H),7.40-7.42 (m, 1H), 7.34 (s, 1H), 7.24 (t, 1H, J=7.5 Hz), 4.57 (s, 2H),3.65 (s, 3H), 3.10-3.46 (m, 1H), 1.881 (d, 3H, J=1.5 Hz), 1.52-1.57 (m,4H), 0.89 (t, 6H, J=7.5 Hz).

Example 382 Synthesis of(Z)-3-(4-{4-[3-(1-ethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1891)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.90-7.98 (m, 3H), 7.73 (s, 1H), 7.41(dd, 1H, J=1.8 Hz, 7.5 Hz), 7.24 (t, 1H, J=7.5 Hz), 6.64 (s, 1H), 4.57(s, 2H), 3.71 (s, 3H), 3.66 (s, 3H), 3.20-3.45 (m, 1H), 1.50-1.59 (m,4H), 0.89 (t, 6H, J=7.2 Hz).

Example 383 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(1-ethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1892)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.96 (dd, 1H, J=1.5 Hz,7.8 Hz), 7.73 (s, 1H), 7.40-7.42 (m, 2H), 7.24 (t, 1H, J=7.5 Hz), 4.57(s, 2H), 3.66 (s, 3H), 3.26-3.38 (m, 1H), 1.69 (s, 3H), 1.50-1.59 (m,4H), 0.89 (t, 6H, J=7.5 Hz).

Example 384 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(1-ethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1893)

1H NMR(DMSO-d6) 12.95 (bs, 2H), 8.24 (s, 2H), 7.96 (dd, 1H, J=1.8 Hz,7.8 Hz), 7.73 (s, 1H), 7.41 (dd, 1H, J=1.5 Hz, 7.5 Hz), 7.24 (t, 1H,J=7.5 Hz), 6.71 (s, 1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.62 (s, 3H),3.24-3.38 (m, 1H), 1.50-1.59 (m, 4H), 0.89 (t, 6H, J=7.5 Hz).

Example 385 Synthesis of(E)-3-{4-[4-(3-cyclohexyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1894)

1H NMR(DMSO-D6) 12.97 (bs, 2H), 7.96 (d, 3H, J=8.4 Hz), 7.74 (s, 1H),7.39-7.7.41 (m, 1H), 7.34 (s, 1H), 7.23 (t, 1H, J=7.8 Hz), 4.59 (s, 2H),3.66 (s, 3H), 3.40-3.44 (m, 1H), 1.91-1.94 (m, 2H), 1.81 (d, 3H, J=1.8Hz), 1.69-1.71 (m, 2H), 1.49-1.51 (m, 1H), 1.25-1.35 (m, 5H).

Example 386 Synthesis of(Z)-3-{4-[4-(3-cyclohexyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1895)

1H NMR(DMSO-d6) 12.94 (bs, 2H), 7.90-7.98 (m, 3H), 7.74 (s, 1H), 7.40(d, 1H, J=7.2 Hz), 7.23 (t, 1H, J=7.8 Hz), 6.65 (s, 1H), 4.59 (s, 2H),3.72 (s, 3H), 3.66 (s, 3H), 3.33-3.43 (m, 1H), 1.91-1.96 (m, 2H),1.69-1.71 (m, 2H), 1.49-1.51 (m, 1H), 1.23-1.35 (m, 5H).

Example 387 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-cyclohexyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1896)

1H NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.97 (d, 1H, J=7.5 Hz),7.73 (s, 1H), 7.38-7.40 (m, 2H), 7.23 (t, 1H, J=7.5 Hz), 4.59 (s, 2H),3.66 (s, 3H), 3.34-3.42 (m, 1H), 1.91-1.96 (m, 2H), 1.69-1.74 (m, 5H),1.48-1.51 (m, 1H), 1.25-1.35 (m, 5H).

Example 388 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclohexyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1897)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 8.24 (s, 2H), 7.96 (d, 1H, J=7.8 Hz),7.73 (s, 1H), 7.39 (d, 1H, J=7.2 Hz), 7.23 (t, 1H, J=7.5 Hz), 6.71 (s,1H), 4.59 (s, 2H), 3.66 (s, 3H), 3.61 (s, 3H), 3.20-3.45 (m, 1H),1.91-1.94 (m, 21), 1.69-1.70 (m, 2H), 1.48-1.51 (m, 1H), 1.25-1.32 (m,5H).

Example 389 Synthesis of(E)-3-[4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]phenyl}-5-methyloxythiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B1898)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.77 (s,1H), 7.76 (d, 1H, J=7.5 Hz), 7.34 (s, 1H), 7.33 (t, 1H, J=7.6 Hz), 7.11(t, 1H, J=7.6 Hz), 4.03 (s, 3H), 3.37 (t, 2H, J=7.0 Hz), 3.03 (s, 2H),2.70 (t, 2H, J=7.0 Hz), 1.80 (s, 3H), 1.70-1.80 (m, 2H,), 0.90 (s, 9H).

Example 390 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]phenyl}-5-methyloxythiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1899)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.20 (s, 2H), 7.77 (s, 1H), 7.76 (d, 1H,J=7.5 Hz), 7.39 (s, 1H), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6 Hz),4.05 (s, 3H), 3.39 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70 (t, 2H, J=7.0Hz), 1.70-1.80 (m, 2H), 1.68 (s, 3H), 0.90 (s, 9H).

Example 391 Synthesis of(Z)-3-[4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]phenyl}-5-methyloxythiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methyloxyacrylicacid (B1900)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.88 (s, 1H), 7.85 (s, 1H), 7.80 (s,1H), 7.76 (d, 1H, J=7.5 Hz), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6Hz), 6.63 (s, 1H), 4.05 (s, 3H), 3.71 (s, 3H), 3.39 (t, 2H, J=7.0 Hz),3.03 (s, 2H), 2.70 (t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H), 0.90 (s, 9H).

Example 392 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy-propyl]phenyl}-5-methyloxythiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1901)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.20 (s, 2H), 7.77 (s, 1H), 7.76 (d, 1H,J=7.5 Hz), 7.33 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6 Hz), 6.63 (s, 1H),4.05 (s, 3H), 3.61 (s, 3H), 3.39 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70(t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H,), 0.90 (s, 9H).

Example 393 Synthesis of(E)-3-[4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]-2-fluorophenyl}-5-methyloxythiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B1902)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.38 (t, 1H,J=7.5 Hz), 7.35 (s, 1H), 7.32 (t, 1H, J=7.6 Hz), 7.11 (t, 1H, J=7.6 Hz),3.95 (s, 3H), 3.37 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70 (t, 2H, J=7.0Hz), 1.76-1.85 (m, 2H), 1.80 (s, 3H), 0.90 (s, 9H).

Example 394 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)propyl]-2-fluorophenyl}-5-methyloxythiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1903)

1H-NMR(DMSO-d6) 12-82 (bs, 1H), 8.28 (s, 2H), 7.40 (t, 1H, J=7.6 Hz),7.39 (s, 1H), 7.25 (t, 1H, J=7.6 Hz), 7.16 (t, 1H, J=7.6 Hz), 3.94 (s,3H), 3.39 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70 (t, 2H, J=7.0 Hz),1.70-1.80 (m, 2H), 1.67 (s, 3H), 0.90 (s, 9H).

Example 395 Synthesis of(Z)-3-[4-(4-{3-[3-(2,2-cdimethylpropyloxy)propyl]-2-fluorophenyl}-5-methyloxythiazol-2-ylcarbamoyl)-2,6-diiluorophenyl]-2-methyloxyacrylic acid (B1904)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7-90 (s, 1H), 7.88 (s, 1H), 7.38 (t, 1H,J=7.5 Hz), 7.29 (t, 1H, J=7.5 Hz), 7.18 (t, 1H, J=7.5 Hz), 6.65 (s, 1H),3.95 (s, 3H), 3.71 (s, 3H), 3.39 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70(t, 2H, J=7.0 Hz), 1.70-1.80 (m, 2H), 0.90 (s, 9H).

Example 396 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{3[3-(2,2-dimethylpropyloxy)propyl]-2-fluorophenyl}-5-methyloxythiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1905)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.20 (s, 2H), 7.40 (t, 1H, J=7.6 Hz),7.29 (t, 1H, J=7.6 Hz), 7.16 (t, 1H, J=7.6 Hz), 6.65 (s, 1H), 3.95 (s,3H), 3.61 (s, 3H), 3.39 (t, 2H, J=7.0 Hz), 3.03 (s, 2H), 2.70 (t, 2H,J=7.0 Hz), 1.70-1.80 (m, 2H), 0.90 (s, 9H).

Example 397 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1906)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.50 (t, 1H,J=7.5 Hz), 7.28-7.38 (m, 3H), 4.27 (s, 1H), 3.95 (s, 3H), 3.17 (s, 3H),1.79 (s, 3H), 0.90 (s, 9H).

Example 398 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1907)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 746-7.52 (m, 1H), 7.38 (s,1H), 7.34-7.38 (m, 2H), 4.27 (s, 1H), 3.95 (s, 3H), 3.17 (s, 3H), 1.69(s, 3H), 0.90 (s, 9H).

Example 399 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (131908)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.50 (m,1H), 7.28-7.38 (m, 2H), 6.65 (s, 1H), 4.27 (s, 1H), 3.95 (s, 3H), 3.70(s, 3H), 3.17 (s, 3H), 0.90 (s, 9H).

Example 400 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxy-2,2-dimethylpropyl)phenyl]-5-methyloxythiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1909)

1H-NMR(DMSO-d6) 12.82 (bs, 1H), 8.28 (s, 2H), 7.46-7.52 (m, 1H),7.34-7.38 (m, 2H), 6.65 (s, 1H), 4.27 (s, 1H), 3.95 (s, 3H), 3.70 (s,3H), 3.17 (s, 3H), 1.69 (s, 3H), 0.90 (s, 9H).

Example 401 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3-ethyloxy-1-methyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1910)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.03 (t, 1H, J=7.2 Hz),7.66 (d, 1H, J=2.4 Hz), 7.32-7.40 (m, 2H), 6.72 (s, 1H), 4.68-4.72 (m,1H), 3.61 (s, 3×), 3.45-3.54 (m, 1H), 3.18 (s, 3H), 1.85-2.01 (m, 2H),1.09 (t, 3H, J=6.9 Hz).

Example 402 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-heptyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1911)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.05 (t, 1H, J=7.5 Hz), 7.88-7.98 (m,2H), 7.65 (d, 1H, J=2.4 Hz), 7.42 (t, 1H, J=6.9 Hz), 7.32 (t, 1H, J=7.5Hz), 6.66 (s, 1H), 4.58 (s, 2H), 3.72 (s, 3H), 3.48 (t, 214, J=6.6 Hz),1.51-1.60 (m, 2H), 1.20-1.40 (m, 5H), 0-85 (t, 3H, J=6.6 Hz).

Example 403 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-heptyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1912)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.25 (s, 2H), 81.04 (dt, 1H, J=1.8, 7.2Hz), 7.65 (d, 1H, J=2.4 Hz), 7.42 (t, 1H, J=6.6 Hz), 7.31 (t, 1H, J=7.5Hz), 6.73 (s, 1H), 4.58 (s, 2H), 3.61 (s, 3H), 3.48 (t, 2H, J=6.6 Hz),1.50-1.58 (m, 2H), 1.20-1.40 (m, 8H), 0.85 (t, 3H, J=6.9 Hz).

Example 404 Synthesis of(Z)-3-{4-[4-(3-ethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (B1913)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.05 (t, 1H, J=7.5 Hz), 7.88-7.96 (m,2H), 7.67 (d, 1H, J=2.4 Hz), 7.44 (t, 1H, J=6.9 Hz), 7.32 (t, 1H, J=7.5Hz), 6.66 (s, 1H), 4.59 (s, 2H), 3.72 (s, 3H), 3.52-3.59 (m, 2H), 1.18(t, 3H, J=6.9 Hz).

Example 405 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-ethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1914)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.04 (dt, 1H, J=2.1, 6.9Hz), 7.66 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=6.3 Hz), 7.31 (t, 1H, J=7.8Hz), 6.73 (s, 1H), 4.59 (s, 2H), 3.61 (s, 3H), 3.52-3.59 (m, 2H), 1.18(t, 3H, J=6.9 Hz).

Example 406 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[1-methyloxy-3-(4-methylpentyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1915)

1H-NMR(DMSO-d6) 13.01 (bs, 2H,), 8.07-7.30 (m, 3H), 7.66 (d, 1H, J=2.7Hz), 7.32-7.42 (m, 3H), 4.69-4.73 (m, 1H), 3.45-3.58 (m, 1H), 3.18 (s,3H), 1.84-2.40 (m, 2H), 1.81 (s, 3H), 1.42-1.54 (m, 3H), 1.12-1.20 (m,2H), 0.84 (d, 6H, J=6.6 Hz).

Example 407 Synthesis of(E)-3-(4-{4-[3-(2-cyclohexylethyloxy)-2-methylphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl-2-methylacrylicacid (B1916)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.90-7.93 (m, 2H), 7.74 (s, 1H),7.63-7.66 (m, 1H), 7.04-7.16 (m, 2H), 6.69 (s, 1H), 4.07 (t, 2H, J=6.7Hz), 3.79 (s, 3H), 3.71 (s, 3H), 0.94-1.80 (m, 16H).

Example 408 Synthesis of(Z)-3-(4-{4-[3-(2-cyclohexylethyloxy)-2-methylphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1917)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.90-7.93 (m, 2H), 7.74 (s, 1H), 7.31(s, 1H), 7.63-7.66 (m, 1H), 7.04-7.16 (m, 2H), 4.07 (t, 2H, J=6.7 Hz),3.79 (s, 3H), 0.94-1.80 (m, 13H).

Example 409 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-cyclohexylethyloxy)-2-methylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1918)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 8.29 (s, 2H), 7.75 (s, 1H), 7.63-7.66(m, 1H), 7.41 (s, 1H), 7.04-7.16 (m, 2H), 4.07 (t, 2H, J=6.4 Hz), 3.79(s, 3H), 3.61 (s, 3H), 0.94-1.80 (m, 16H).

Example 410 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-cyclohexylethyloxy)-2-methylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1919)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 8.25 (s, 2H), 7.74 (s, 1H), 7.63-7.66(m, 1H), 7.04-7.16 (m, 2H), 6.74 (s, 1H), 4.07 (t, 2H, J=6.4 Hz), 3.79(s, 3H), 3.61 (s, 3H), 0.94-1.80 (m, 13H).

Example 411 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[2-(4-methylpentyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1920)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.94-7.97 (m, 2H), 7.85-7.88 (m, 1H),7.72 (s, 1H), 7.34 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H),3.59-3.65 (m, 5H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz), 1.81 (s,3H), 1.44-1.53 (m, 3H), 1.12-1.20 (m, 2H), 0.84 (d, 6H, J=6.7 Hz).

Example 412 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[2-(4-methylpentyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1921)

1H-NMR(DMSO-d6) 13.57 (bs, 1H), 12.97 (bs, 1H), 7.85-7.92 (m, 3H), 7.72(s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.66 (s, 1H), 3.71 (s,3H), 3.59-3.65 (m, 2H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz),1.44-1.53 (m, 3H), 1.12-1.20 (m, 2H), 0&84 (d, 6H, J=6.7 Hz).

Example 413 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-methyloxy-3-[2-(4-methylpentyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1922)

¹H-NMR(DMSO-D6) 12.97 (bs, 2H), 8.29 (s, 2H), 7.86-7.88 (m, 1H), 7.72(s, 1H), 7.40 (s, 1H), 7.27-7.29 (m, 1H), 7.13-7.18 (m, 1H), 3.60-3.64(m, 5H), 3.36-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz), 1.69 (s, 3H),1.44-1.53 (m, 3H), 1.12-1.20 (m, 2H), 0.84 (d, 6H, J=6.7 Hz).

Example 414 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{2-methyloxy-3-[2-(4-methylpentyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1923)

1H-NMR(DMSO-d6) 13.57 (bs, 1H), 12.97 (bs, 1H), 8.25 (s, 2H), 7.85-7.88(m, 1H), 7.72 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.74 (s,1H), 3.59-3.65 (m, 8H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz),1.46-1.51 (m, 3H), 1.12-1.19 (m, 2H), 0.83 (d, 6H, J=6.6 Hz).

Example 415 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(2-pentyloxyethyl)phenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1924)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.98 (m, 2H), 7.85-7.88 (m, 1H),7.72 (s1H), 7.34 (s, 1H), 7.27-7.29 (m, 1H), 7.14-7.19 (m, 1H),3.59-3.65 (m, 5H), 3.36-3.41 (m, 2H), 2.91 (t, 2H, J=7.4 Hz), 1.81 (s,3H), 1.44-1.49 (m, 2H), 1.24-1.27 (m, 4H), 0.82-0.87 (m, 3H).

Example 416 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(2-pentyloxyethyl)phenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1925)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.29 (s, 2H), 7.85-7.88 (m, 1H), 7.72(s1H), 7.41 (s, 1H), 7.27-7.29 (m, 1H), 7.13-7.19 (m, 1H), 3.59-3.65 (m,5H), 3.36-3.41 (m, 2H), 2.91 (t, 2H, J=7.4 Hz), 1.69 (s, 3H), 1.44-1.49(m, 2H), 1.24-1.27 (m, 4H), 0.82-0.87 (m, 3H).

Example 417 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-(2-hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1926)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 7.95-7.98 (m, 2H), 7.85-7.89 (m, 1H),7.72 (s, 1H), 7.40 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H),3.59-3.64 (m, 5H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz), 1.81 (s,3H), 1.44-1.49 (m, 2H), 1.24-1.27 (m, 6H), 0.82-0.87 (m, 3H).

Example 418 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[3-(2-hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1927)

1H-NMR(DMSO-d6) 13.55 (bs, 1H), 12.98 (bs, 1H), 7.85-7.92 (m, 3H), 7.72(s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H), 6.66 (s, 1H), 3.71 (s,3H), 3.59-3.64 (m, 5H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz),1.44-1.49 (m, 2H), 1.24-1.27 (m, 6H), 0.82-0.87 (m, 3H).

Example 419 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1928)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.85-7.88 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H), 3.59-3.65(m, 5H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.0 Hz), 1.69 (s, 3H),1.44-1.49 (m, 2H), 1.24-1.27 (m, 6H), 0.82-0.87 (m, 3H).

Example 420 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-hexyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1929)

1H-NMR(DMSO-d6) 13.57 (bs, 1H), 12.97 (bs, 1H), 8.24 (s, 2H), 7.85-7.88(m, 1H), 7.72 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.73 (s,1H), 3.59-3.65 (m, 8H), 3.37-3.41 (m, 2H), 2.91 (t, 2H, J=7.4 Hz),1.44-1.49 (m, 2H), 1.24-1.27 (m, 6H), 0.82-0.87 (m, 3H).

Example 421 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{2-fluoro-3-[1-methyloxy-3-(4-methylpentyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1930)

1H-NMR(DMSO-d6) 12.98 (bs, 1H), 8.03 (dt, 1H, J=3.3, 6.6 Hz), 7.87-7.96(m, 2H), 7.65 (d, 1H, J=2.1 Hz), 7.31-7.41 (m, 2H), 6.64 (s, 1H),4.68-4.73 (m, 1H), 3.17 (s, 3H), 3.45-3.58 (m, 1H), 3.18 (s, 3H),1.86-1.93 (m, 2H), 1.41-1.57 (m, 3H), 1.12-1.22 (m, 2H), 0.84 (d, 6H,J=6.6 Hz).

Example 422 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[1-methyloxy-3-(4-methylpentyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1931)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.03 (dt, 1H, J=2.1, 7.5Hz), 7.65 (d, 1H, J=2.7 Hz), 7.31-7.44 (m, 3H), 4.68-4.73 (m, 1H), 3.18(s, 3H), 1.86-2.05 (m, 2H), 1.69 (s, 3H), 1.41-1.56 (m, 3H), 1.12-1.29(m, 2H), 0.84 (d, 6H, J=6.6 Hz).

Example 423 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{2-fluoro-3-[1-methyloxy-3-(4-methylpentyloxy)propyl]phenyl}thiazol-2-ylcarbamoyl)phenyl)-2-methyloxyacrylicacid (B1932)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 1H), 8.03 (dt, 1H, J=3.3, 6.6Hz), 7.65 (d, 1H, J=2.4 Hz), 7.31-7.40 (m, 2H), 6.71 (s, 1H), 4.68-4.73(m, 1H), 3.61 (s, 3H), 3.45-3.54 (m, 1H), 3.18 (s, 3H), 1.85-2.01 (m,2H), 1.41-1.55 (m, 311, 1.12-1.20 (m, 2H), 0.84 (d, 6H, J=6.3 Hz).

Example 424 Synthesis of(E)-3-(4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1933)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.93-7.97 (m, 3H), 7.72 (s, 1H), 7.38(dd, 1H, J=1.5 Hz, 7.5 Hz), 7.32 (s, 1H), 7.23 (t, 1H, J=7.5 Hz), 4.58(s, 2H), 3.64 (s, 3H), 3.18 (s, 2H), 1.79 (d, 3H, J=1.2 Hz), 0.91 (s,9H).

Example 425 Synthesis of(E)-3-(4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1934)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 7.96 (d, 3H, J=7.8 Hz), 7.74 (s, 1H),7.34-7.39 (m, 2H), 7.24 (t, 1H, J=7.8 Hz), 4.56 (s, 2H), 3.66 (s, 3H),3.57 (t, 2H, J=7.2 Hz), 1.81 (s, 3H), 1.53 (t, 2H, J=7.2 Hz), 0.92 (s,9H).

Example 426 Synthesis of(Z)-3-(4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1935)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.88-7.98 (m, 3H), 7.73 (s, 1H), 7.37(dd, 114, J=1.8 Hz, 7.5 Hz), 7.23 (t, 1H, J=7.5 Hz), 6.65 (s, 1H), 4.56(s, 2H), 3.71 (s, 3H), 3.65 (s, 3H), 3.57 (t, 2H, J=7.2 Hz), 1.53 (t,2H, J=7.2 Hz), 0.92 (s, 9H).

Example 427 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1936)

1H NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.97 (d, 1H, 7.2 Hz), 7.73(s, 1H), 7.37-7.40 (m, 2H), 7.23 (t, 1H, J=7.2 Hz), 4.56 (s, 2H), 3.65(s, 3H), 3.57 (t, 2H, J=7.2 Hz), 1.69 (s, 3H), 1.52 (t, 2H, J=7.5 Hz),0.92 (s, 9H).

Example 428 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1937)

1H NMR(DMSO-d6) 12.97 (bs, 2H), 8.25 (s, 2H), 7.97 (d, 1H, J=7.8 Hz),7.74 (s, 1H), 7.38 (d, 1H, J=7.2 Hz), 7.24 (t, 1H, J=7.5 Hz), 6.72 (s,1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.63 (s, 3H), 3.58 (t, 2H, J=7.2 Hz),1.53 (t, 2H, J=7.5 Hz), 0.92 (s, 9H).

Example 429 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(4-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1938)

1H NMR(DMSO-d6) 12.99 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.34-7.39 (m, 2H), 7.24 (t, 1H, J=7.8 Hz), 4.56 (s, 2H), 3.65 (s, 3H),3.49 (t, 2H, J=6.9 Hz), 1181 (s, 3H), 1.49-1.62 (m, 3H), 1.19-1.26 (m,2H), 0.87 (d, 6H, J=6.6 Hz).

Example 430 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(4-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1939)

1H NMR(DMSO-D6) 12.94 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H),7.37-7.39 (m, 1H), 7.24 (t, 1H, J=7.8 Hz), 6.66 (s, 1H), 4.56 (s, 2H),3.72 (s, 3H), 3.65 (s, 3H), 3.49 (t, 2H, J=6.6 Hz), 1.49-1.62 (m, 3H),1.19-1.26 (m, 2H), 0.87 (d, 6H, J=6.6 Hz).

Example 431 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(4-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1940)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.98 (d, 1H, J=7.8 Hz),7.74 (s, 1H), 7.37-7.40 (m, 2H), 7.24 (t, 1H, J=7.5 Hz), 4.56 (s, 2H),3.66 (s, 3H), 3.49 (t, 2H, J=6.6 Hz), 1.69 (s, 3H), 1.49-1.62 (m, 3H),1.19-1.26 (m, 2H), 0.87 (d, 6H, J=6.6 Hz).

Example 432 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(4-pentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1941)

1H NMR(DMSO-D6) 12.97 (bs, 2H), 8.25 (s, 2H), 7.97 (dd, 1H, J=1.5 Hz,7.8 Hz), 7.74 (s, 1H), 7.37-7.39 (m, 1H), 7.24 (t, 1H, J=7.8 Hz), 6.73(s, 1H), 4.56 (s, 2H), 3.65 (s, 3H), 3.63 (s, 3H), 3.49 (t, 2H, J=6.6Hz), 1.49-1.62 (m, 3H), 1.15-1.26 (m, 2H), 0.87 (d, 6H, J=6.6 Hz).

Example 433 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-ethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylic acid (B1942)

1H-NMR(CDCl₃-d6) 8.32 (s, 2H), 7.65 (d, 1H, J=1.2 Hz), 7.49 (dd, 1H,J=7.8, 1.8 Hz), 7.45 (s, 1H), 7.24-7.28 (m, 1H), 7.16 (t, 1H, J=7.8 Hz),3.57 (s, 3H), 3.46-3.53 (m, 4H), 2.75-2.82 (m, 2H), 1.91-2.05 (m, 2H),1.86 (d, 3H, J=1.5 Hz), 1.22 (t, 3H, J=6.9 Hz).

Example 434 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3-ethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1943)

H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.24 (s, 2H), 7.85 (dd, 1H, J=7.8, 2.1Hz), 7.72 (s, 1H), 7.13-7.24 (m, 2H), 6.73 (s, 1H), 3.61 (s, 6H),3.39-3.47 (m, 4H), 2.68-2.75 (m, 2H), 1.78-1.90 (m, 2H), 1.13 (t, 3H,J=6.9 Hz).

Example 435 Synthesis of(E)-3-(4-{4-[3-(3-cyclopropylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1944)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.86 (d, 1H,J=7.8 Hz), 7.73 (s, 1H), 7.34 (bs, 1H), 7.13-7.26 (m, 2H), 3.61 (s, 3H),3.44 (t, 2H, J=6.0 Hz), 3.23 (d, 1H, J=6.9 Hz), 2.72 (t, 2H, J=8.4 Hz),1.80-1.90 (m, 5H), 0.94-1.10 (m, 1H), 0.42-0.53 (m, 2H), 0.16-0.21 (m,2H).

Example 436 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-cyclopropylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1945)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.86 (d, 1H, J=7.8 Hz),7.72 (bs, 1H), 7.41 (s, 1H), 7.13-7.26 (m, 2H), 3.62 (s, 3H), 3.44 (t,2H, J=6.3 Hz), 3.23 (d, 2H, J=6.9 Hz), 2.72 (t, 2H, J=8.4 Hz), 1.80-1.93(m, 2H), 1.69 (s, 3H), 0.96-1.08 (m, 1H), 0.45-0.54 (m, 2H), 0.16-0.25(m, 2H).

Example 437 Synthesis of(Z)-3-(4-{4-[3-(3-cyclopropylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylic acid (B1946)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 7.83-7.96 (m, 3H), 7.72(s, 1H), 7.13-7.26 (m, 2H), 6.66 (s, 1H), 3.71 (s, 3H), 3.61 (s, 3H),3.44 (t, 2H, J=6.3 Hz), 3.23 (d, 2H, J=6.9 Hz), 2.72 (t, 2H, J=8.7 Hz),1.79-1.89 (m, 2H), 0.97-1.06 (m, 1H), 0.43-0.50 (m, 2H), 0.14-0.21 (m,2H).

Example 438 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3-cyclopropylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (13947)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.25 (s, 2H), 8.36 (d, 1H, J=8.4 Hz),7.73 (s, 1H), 7.13-7.26 (m, 2H), 6.73 (s, 1H), 3.61 (s, 6H), 3.44 (t,2H, J=5.7 Hz), 3.23 (d, 2H, J=6.6 Hz), 2.69-2.76 (m, 2H), 1.78-1.88 (m,2H), 0.97-1.15 (m, 1H), 0.44-0.51 (m, 2H), 0.16-0.20 (m, 2H).

Example 439 Synthesis of(E)-3-(4-{4-[3-(3-cyclopentylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1948)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.85 (dd, 1H,J=7.5, 1.8 Hz), 7.73 (s, 1H), 7.34 (bs, 1H), 7.13-7.25 (m, 2H), 3.61 (s,3H), 3.43 (t, 2H, J=6 Hz), 3.25 (d, 2H, J=6.9 Hz), 2.72 (t, 2H, J=9.0Hz), 2.06-2.16 (m, 1H), 2.48-2.54 (m, 51), 1.46-1.76 (m, 6H), 1.16-1.30(m, 2H).

Example 440 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3-cyclopentylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1949)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.86 (d, 1H, J=7.2 Hz),7.72 (s, 1H), 7.40 (s, 1H), 7.13-7.25 (m, 2H), 3.61 (s, 3H), 3.43 (t,2H, J=6.3 Hz), 3.25 (d, 2H, J=6.9 Hz), 2.69-2.78 (m, 2H), 2.06-2.16 (m,1H), 1.80-1.90 (m, 2H), 1.64-1.76 (m, 5H), 1.46-1.60 (m, 4H), 1.08-1.12(m, 2H).

Example 441 Synthesis of(Z)-3-(4-{4-[3-(3-cyclopentylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1950)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 7.83-7.96 (m, 3H), 7.72(s, 1H), 7.13-7.26 (m, 2H), 6.66 (s, 1H), 3.71 (s, 3H), 3.61 (s, 3H),3.43 (t, 2H, J=6.0 Hz), 3.25 (d, 2H, J=6.9 Hz), 2.72 (t, 2H, J=6.3 Hz),2.06-2.16 (m, 1H), 1.78-1.90 (m, 2H), 1.62-1.75 (m, 2H), 1.44-1.60 (m,4H), 1.18-1.21 (m, 2H).

Example 442 Synthesis of(Z)-3-(2,6-dichloro-4-{-4-[3-(3-cyclopentylmethyloxypropyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1951)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.24 (s, 2H), 7.86 (d, 1H, J=7.5 Hz),7.72 (s, 1H), 7.13-7.25 (m, 2H), 6.73 (s, 1H), 3.43 (t, 2H, J=6.3 Hz),3.25 (d, 2H, J=6.9 Hz), 2.72 (t, 2H, J=8.4 Hz), 2.06-2.17 (m, 1H),1.80-1.90 (m, 2H), 1.62-1.76 (m, 2H), 1.46-1.60 (m, 4H), 1.17-1.30 (m,2H).

Example 443 Synthesis of(E)-3-(2,6-difluoro-4-{4-[3-(2-heptyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1952)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.99 (m, 2H), 7.85-7.88 (m, 1H),7.72 (s, 1H), 7.34 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H),3.59-3.65 (m, 5H), 3.40 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.81(d, 3H, J=1.5 Hz), 1.48 (t, 2H, J=6.6 Hz), 1.24 (bs, 8H), 0.82-0.88 (m,3H).

Example 444 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[3-(2-heptyloxyethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1953)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.85-7.92 (m, 3H), 7.72 (s, 1H),7.26-7.29 (m, 1H), 7.13-7.18 (m, 1H), 6.66 (s, 1H), 3.71 (s, 3H),3.59-3.64 (m, 5H), 3.40 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz),1.46-1.51 (m, 2H), 1.24 (bs, 8H), 0.82-0.87 (m, 3H).

Example 445 Synthesis of(E)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[2-(3-methylbutyloxyethyl)phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1954)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 7.95-7.97 (m, 2H), 7.85-7.88 (m, 1H),7.72 (s, 1H), 7.34 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H),3.59-3.65 (m, 5H), 3.43 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.81(s, 3H), 1.58-1651 (m, 1H), 1.36-1.42 (m, 2H), 0.85 (d, 6H, J=6.6 Hz).

Example 446 Synthesis of(E)-3-[2,6-dichloro-4-(4-{2-methyloxy-3-[2-(3-methylbutyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1955)

1H-NMR(DMSO-d6) 12.98 (s, 2H), 8.29 (s, 2H), 7.85-7.88 (m, 1H), 7.72 (s,1H), 7.41 (s, 1H), 7.27-7.29 (m, 1H), 7.14-7.19 (m, 1H), 3.60-3.66 (m,5H), 3.43 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=7.0 Hz), 1.59-1.69 (m, 4H),1.36-1.40 (m, 2H), 0.85 (d, 6H, J=6.6 Hz).

Example 447 Synthesis of(Z)-3-[2,6-difluoro-4-(4-{2-methyloxy-3-[2-(3-methylbutyloxy)ethyl]phenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1956)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.86-7.93 (m, 3H), 7.72 (s, 1H),7.27-7.29 (m, 1H), 7.13-7.19 (m, 1H), 6.67 (s, 1H), 3.71 (s, 3H),3.62-3.64 (m, 5H), 3.43 (t, 2H, J=6.9 Hz), 2.91 (t, 2H, J=6.6 Hz),1.58-1.67 (m, 1H), 1.35-1.42 (m, 2H), 0.85 (d, 6H, J=6.4 Hz).

Example 448 Synthesis of(E)-3-(4-{4-[3-(2-cyclohexylmethyloxyethyl)-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl)-2-methylacrylicacid (B1957)

¹H-NMR(DMSO-D6) 12.98 (bs, 2H), 7.95-7.98 (m, 1H), 7.85-7.89 (m, 1H),7.73 (s, 1H), 7.34 (s, 1H), 7.26-7.29 (m, 1H), 7.14-7.19 (m, 1H),3.59-3.65 (m, 5H), 3.23 (d, 2H, J=6.3 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.81(d, 3H, J=1.5 Hz), 1.63-1.68 (m, 6H), 1.08-1.21 (m, 2H), 0.87-0.94 (m,1H).

Example 449 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[2-(2-ethylbutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B 1958)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.85-7.89 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.27-7.30 (m, 1H), 7.14-7.19 (m, 1H), 3.60-3.66(m, 5H), 3.30-3.32 (m, 2H), 2.91 (t, 2H, J=6.9 Hz), 1.69 (s, 3H),1.22-1.40 (m, 5H), 0.82 (t, 6H, J=7-5 Hz).

Example 450 Synthesis of(E)-3-[4-(4-{3-[2-(2-ethylbutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B1959)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.95-7.98 (m, 2H), 7.85-7.89 (m, 1H),7.72 (s, 1H), 7.42 (s, 1H), 7.27-7.29 (m, 1H), 7.13-7.19 (m, 1H),3.60-3.65 (m, 5H), 3.30-3.32 (m, 2H), 2.91 (t, 2H, J=6.9 Hz), 1.81 (s,3H), 1.22-1.40 (m, 5H), 0.82 (t, 6H, J=7.3 Hz).

Example 451 Synthesis of(Z)-3-[2,6-d]chloro-4-(4-{3-[2-(2-ethylbutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1960)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.24 (s, 1H), 7.85-7.88 (m, 1H), 7.72(s, 1H), 7.27-7.30 (m, 1H), 7.13-7.18 (m, 1H), 6.73 (s, 1H), 3.60-3.64(m, 8H), 3.30-3.33 (m, 2H), 2.91 (t, 2H, J=6.7 Hz), 1.22-1.40 (m, 5H),0.82 (t, 6H, J=7.3 Hz).

Example 452 Synthesis of(E)-3-[4-(4-{3-[2-(4-chlorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B1961)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.95-7.98 (m, 2H), 7.86-7.88 (m, 1H),7.72 (s, 1H), 7.26-7.41 (m, 2H), 7.14-7.19 (m, 1H), 3.61-3.65 (m, 7H),3.44 (t, 2H, J=6.3 Hz), 2.91 (t, 2H, J=6.9 Hz), 1.70-1.81 (m, 5H),1.60-1.66 (m, 2H).

Example 453 Synthesis of(Z)-3-[4-(4-{3-[2-(4-chlorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methyloxyacrylicacid (B1962)

¹H-NMR(DMSO-D6) 12.91 (bs, 2H), 7.85-7.92 (m, 3H), 7.72 (s, 1H),7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H), 6.66 (s, 1H), 3.71 (s, 3H),3.60-3.65 (m, 7H), 2.91 (t, 2H, J=6.9 Hz), 1.72-1.77 (m, 2H), 1.59-1.63(m, 2H).

Example 454 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[2-(4-chlorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B1963)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.86-7.88 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.27-7.29 (m, 1H), 7.14-7.19 (m, 1H), 3.61-3.66(m, 7H), 3.46 (t, 2H, J=6.1 Hz), 2.91 (t, 2H, J=6.7 Hz), 1.59-1.77 (m,7H).

Example 455 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{3-[2-(4-chlorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B1964)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.24 (s, 2H), 7.86-7.88 (m, 1H), 7.72(s, 1H), 7.27-7.29 (m, 1H), 7.14-7.19 (m, 1H), 6.73 (s, 1H), 3.61-3.65(m, 10H), 3.42-3.46 (m, 2H), 2.90-2.94 (m, 2H), 1.58-1.77 (m, 5H).

Example 456 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-isobutyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1965)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H), 3.09-3.16 (m, 2H),1.85-1.95 (m, 2H), 1.79 (s, 3H), 1.74-1.79 (m, 1H), 0.85 (d, 6H, J=6.0Hz).

Example 457 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isobutyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1966)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.50-3.58 (m,1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H), 3.09-3.16 (m, 2H), 1.85-1.95 (m,2H), 1.74-1.79 (m, 1H), 1.68 (s, 3H), 0.85 (d, 6H, J=6.0 Hz).

Example 458 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-isobutyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1967)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,111, J=6.5 Hz), 3.71 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17(s, 3H), 3.09-3.16 (m, 2H), 1.85-1.95 (m, 2H), 1.74-1.79 (m, 1H), 0.85(d, 6H, J=6.0 Hz).

Example 459 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isobutyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1968)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.06 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.72 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.61 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H),3.09-3.16 (m, 2H), 1.85-1.95 (m, 2H), 1.74-1.79 (m, 1H), 0.85 (d, 6H,J=6.0 Hz).

Example 460 Synthesis of(E)-3-(4-{4-[3-(2-ethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1969)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.04 (dt, 1H, J=1.5, 7.5 Hz), 7.92-8.00(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.43 (dt, 1H, J=2.1, 7.5 Hz), 7.34 (s,1H), 7.31 (t, 1H, J=7.5 Hz), 4.59 (s, 2H), 1.81 (s, 3H), 1.25-1.49 (m,5H), 0.84 (t, 6H, J=7.5 Hz).

Example 461 Synthesis of(Z)-3-(4-{4-[3-(2-ethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1970)

¹H-NMR(DMSO-D6) 12.98 (bs, 1H), 8.04 (t, 1H, J=1.8, 7.8 Hz), 7.87-7.95(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=6.6 Hz), 7.31 (t, 1H,J=7.5 Hz), 6.64 (s, 1H), 4.59 (s, 2H), 3.71 (s, 3H), 3.40 (d, 2H, J=5.7Hz), 1.25-1.49 (m, 5H), 0.84 (t, 6H, J=7.5 Hz).

Example 462 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-ethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1971)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=1.5, 7.5Hz), 7.64 (d, 1H, J=2.4 Hz), 7.38-7.46 (m, 2H), 7.31 (t, 1H, J=7.5 Hz),4.59 (s, 2H), 3.40 (d, 2H, J=5.7 Hz), 1.69 (s, 3H), 1.25-1.49 (m, 5H),0.84 (t, 6H, J=7.5 Hz).

Example 463 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-ethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1972)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.24 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.8Hz), 7.65 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=6.6 Hz), 7.31 (t, 1H, J=7.5Hz), 6.71 (s, 1H), 4.59 (s, 2H), 3.61 (s, 3H), 3.40 (d, 2H, J=5.4 Hz),1.25-1.49 (m, 5H), 0.84 (t, 6H, J=7.5 Hz).

Example 464 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-isobutyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1973)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.04 (dt, 1H, J=1.8, 7.8 Hz), 7.92-8.00(m, 2H), 7.65 (d, 1H, J=2.4 Hz), 7.43 (t, 1H, J=6.0 Hz), 7.34 (s, 1H),7.32 (t, 1H, J=7.5 Hz), 4.60 (s, 2H), 1.80-1.93 (m, 1H), 1.81 (s, 3H),0.89 (d, 6H, J=6.6 Hz).

Example 465 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-isobutyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1974)

1H-NMR(DMSO-d6) 12.98 (bs, 1H), 8.04 (dt, 1H, J=1.8, 7.5 Hz), 7.87-7.95(m, 2H), 7.65 (d, 1H, J=2.4 Hz), 7.43 (dt, 1H, J=1.8, 6.6 Hz), 7.32 (t,1H, J=7.5 Hz), 6.66 (s, 1H), 4.59 (s, 2H), 3.71 (s, 3H), 1.80-1.93 (m,1H), 0.89 (d, 611, J=6.9 Hz).

Example 466 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-isobutyloxymethylphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1975)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=2.1, 7.8Hz), 7.65 (d, 1H, J=2.7 Hz), 7.38-7.46 (m, 2H), 7.32 (t, 1H, J=7.5 Hz),4.60 (s, 2H), 1.82-1.91 (m, 1H), 1.69 (s, 3H), 0.89 (d, 6H, J=6.6 Hz).

Example 467 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-isobutyloxymethylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1976)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.25 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.8Hz), 7.66 (d, 1H, J=2.4 Hz), 7.44 (t, 1H, J=6.6 Hz), 7.32 (t, 1H, J=7.5Hz), 6.72 (s, 1H), 4.60 (s, 2H), 3.62 (s, 3H), 1.82-1.89 (m, 1H), 0.89(d, 6H, J=6.9 Hz).

Example 468 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1977)

1H-NMR(DMSO-d6) 12.98 (bs, 1H), 8.04 (dt, 1H, J=1.5, 7.2 Hz), 7.86-7.96(m, 2H), 7.66 (d, 1H, J=2.4 Hz), 7.43 (d, 1H, J=6.0 Hz), 7.31 (t, 1H,J=7.5 Hz), 6.65 (s, 1H), 4.59 (s, 2H), 3.72 (s, 3H), 3.52 (t, 2H, J=6.6Hz), 1.63-1.76 (m, 1H), 1.42-1.49 (m, 2H), 0.88 (d, 6H, J=6.6 Hz).

Example 469 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1978)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.25 (s, 2H), 8.04 (dt, 1H, J=1.5, 7.5Hz), 7.65 (d, 1H, J=2.4 Hz), 7.42 (t, 1H, J=6.9 Hz), 7.31 (t, 1H, J=7.2Hz), 6.72 (s, 1H), 4.58 (s, 2H), 3.61 (s, 3H), 3.52 (t, 2H, J=6.6 Hz),1.62-1.76 (m, 1H), 1.42-1.49 (m, 2H), 0.88 (d; 6H, J=6.6 Hz).

Example 470 Synthesis of(E)-3-{4-[4-(3-cyclobutylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl)-2-methylacrylicacid (B1979)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.04 (dt, 1H, J=2.1, 7.8 Hz), 7.92-8.00(m, 2H), 7.65 (d, 1H, J=2.4 Hz), 7.42 (dt, 1H, J=1.8, 6.9 Hz), 7.34 (s,1H), 7.31 (t, 1H, J=7.8 Hz), 4.59 (s, 2H), 3.48 (d, 2H, J=6.6 Hz),2.50-2.61 (m, 1H), 1.64-2.04 (m, 9H).

Example 471 Synthesis of(Z)-3-{4-[4-(3-cyclobutylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1980)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.04 (dt, 1H, J=1.8, 7.8 Hz), 7.86-7.95(m, 2H), 7.65 (d, 1H, J=2.4 Hz), 7.43 (dt, 1E, J=1.8, 7.5 Hz), 7.31 (t,1H, J=7.5 Hz), 6.65 (s, 1H), 4.60 (s, 2H), 3.71 (s, 3H), 3.48 (d, 2H,J=6.6 Hz), 2.50-2.61 (m, 1H), 1.67-2.05 (m, 6H).

Example 472 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-cyclobutylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl)-2-methylacrylicacid (B1981)

1H-NMR(DMSO-d6) 13.03 (bs, 2H), 8-29 (s, 2H), 8.04 (t, 1H, J=7.2 Hz),7.65 (d, 1H, J=2.7 Hz), 7.38-7.48 (m, 2H), 7.31 (t, 1H, J=7.8 Hz), 4.60(s, 2H), 3.47 (d, 2H, J=6.6 Hz), 1.62-2.03 (m, 6H), 1.69 (s, 3H).

Example 473 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclobutylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl)-2-methyloxyacrylicacid (B1982)

1H-NMR(DMSO-d6) 13.00 (bs, 1H), 8.24 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.5Hz), 7.65 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=6.3 Hz), 7.31 (t, 1H, J=7.5Hz), 6.72 (s, 1H), 4.60 (s, 2H), 3.61 (s, 3H), 3.48 (d, 2H, J=6.9 Hz),2.48-2.52 (m, 1H), 2.05-1.67 (m, 6H).

Example 474 Synthesis of(E)-3-(4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1983)

1H-NMR(DMSO-d6) 13.01 (bs, 2H), 7.92-8.08 (m, 2H), 7.65 (d, 1H, J=2.4Hz), 7.44 (t, 1H, J=5.4 Hz), 7.34 (d, 1H, J=2.4 Hz), 7.32 (t, 1H, J=7.5Hz), 4.62 (s, 2H), 3.18 (s, 2H), 1.81 (s, 3H), 0.91 (s, 9H).

Example 475 Synthesis of(Z)-3-(4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B1984)

1H-NMR(DMSO-D6) 12.98 (bs, 1H), 8.04 (Dt, 1H, J=1.8, 7.5 Hz), 7.87-7.94(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.45 (dt, 1H, J=1.8, 6.6 Hz), 7.32 (t,1H, J=7.5 Hz), 6.66 (s, 1H), 4.62 (s, 2H), 3.61 (s, 3H), 3.18 (s, 2H),0.91 (s, 9E).

Example 476 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B1985)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.5Hz), 7.63 (d, 1H, J=2.4 Hz), 7.44 (dt, 1H, J=2.1, 8.4 Hz), 7.40 (d, 1H,J=1.2 Hz), 7.32 (t, 1H, J=7.8 Hz), 4.62 (s, 2H), 3.18 (s, 2H), 1.39 (s,3H), 0.91 (s, 9H).

Example 477 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2,2-dimethyl-propyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1986)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.24 (s, 2H), 8.04 (dt, 1H, J=1.5, 7.2Hz), 7.65 (d, 1H, J=2.7 Hz), 7.43 (t, 1H, J=6.6 Hz), 7.32 (t, 1H, J=7.5Hz), 6.72 (s, 1H), 4.62 (s, 2H), 3.61 (s, 3H), 3.18 (s, 2H), 0.91 (s,9H).

Example 478 Synthesis of(E)-3-(4-{4-[3-(2-cyclopentyethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B1987)

1H-NMR(DMSO-d6) 12.99 (bs, 2H), 8.04 (dt, 1H, J=1.8, 7.8 Hz), 7.92-8.02(m, 2H), 7.66 (d, 1H, J=2.7 Hz), 7.39-7.46 (m, 1H), 7.28-7.36 (m, 2H),4.59 (s, 2H), 3.51 (t, 2H, J=6.9 Hz), 1.45-1.95 (m, 11H), 1.00-1.18 (m,2H).

Example 479 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-cyclopentyethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl)phenyl)-2-methylacrylicacid (B1988)

1H-NMR(DMSO-d6) 13.04 (bs, 2H), 8.29 (s, 2H), 8.01-8.07 (m, 1H), 7.65(d, 111, J=2.4 Hz), 7.38-7.47 (m, 2H), 7.31 (t, 1H, J=7.8 Hz), 4.59 (s,2H), 3.51 (t, 2H, J=6.6 Hz), 1.65-1.90 (m, 6H), 1.40-1.65 (m, 5H),1.00-1.17 (m, 2H).

Example 480 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-cyclopentyethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B1989)

1H-NMR(DMSO-d6) 12.85 (bs, 1H), 8.07 (s, 2H), 7.87 (dt, 1H, J=1.8, 7.8Hz), 7.48 (d, 1H, J=1.8 Hz), 7.22-7.30 (m, 1H), 7.14 (t, 1H, J=7.8 Hz),6.55 (s, 1H), 4.41 (s, 2H), 3.44 (s, 3H), 3.33 (t, 2H, J=6.6 Hz),1.26-1.73 (m, 9H), 0.86-1.00 (m, 2H).

Example 481 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-heptyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B31990)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.98 (m, 3H), 7.74 (s, 1H),7.34-7.39 (m, 2H), 7.21-7.26 (m, 1H), 4.56 (s, 2H), 3.65 (s, 3H), 3.50(t, 2H, J=6.0 Hz), 1.81 (s, 3H), 1.54-1.56 (m, 2H), 1.25 (bs, 8H),0.83-0.86 (m, 3H).

Example 482 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-heptyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1991)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.96-7.99 (m, 1H), 7.74(s, 1H), 7.36-7.41 (m, 2H), 7.21-7.26 (m, 1H), 4.56 (s, 2H), 3.66 (s,3H), 3.50 (t, 2H, J=6.0 Hz), 169 (s, 3H), 1.52-1.59 (m, 2H), 1.25 (bs,8H), 0.83-0.88 (m, 3H).

Example 483 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-hexyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1992)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.34-7.39 (m, 2H), 7.21-7.26 (m, 1H), 4.56 (s, 2H), 3.65 (s, 3H), 3.50(t, 2H, J=6.0 Hz), 1.81 (s, 3H), 1.52-1.59 (m, 2H), 1.27-1.36 (m, 6H),0.84-0.88 (m, 3H).

Example 484 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-hexyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1993)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 8.29 (s, 2H), 7.96-7.98 (m, 1H), 7.73(m, 1H), 7.36-7.40 (m, 2H), 7.21-7.26 (m, 1H), 4.56 (s, 2H), 3.65 (s,3×), 3.50 (t, 2H, J=6.0 Hz), 1.69 (s, 3H), 1.52-1.59 (m, 2H), 1.26-1.36(m, 6H), 0.84-0.88 (m, 3H).

Example 484 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-hexyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B1994)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.25 (s, 2H), 7.96-7.99 (m, 1H), 7.73(s, 1H), 7.36-7.39 (m, 1H), 7.21-7.27 (m, 1H), 6.73 (s, 1H), 4.56 (s,2H), 3.65 (s, 3H), 3.62 (s, 3H), 3.50 (t, 2H, J=6.3 Hz), 1.52-1.59 (m,2H), 1.26-1.36 (m, 6H), 0.84-0.88 (m, 3H)

Example 486 Synthesis of(E)-3-{4-[4-(3-butyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]-2,6-dichlorophenyl}-2-methylacrylicacid (B1995),

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.96-7.99 (m, 1H), 7.74(s, 1H), 7.37-7.41 (m, 2H), 7.21-7.26 (m, 1H), 4.56 (s, 2H), 3.66 (s,3H), 3.51 (t, 2H, J=6.3 Hz), 1.69 (s, 3H), 1.51-1.60 (m, 2H), 1.30-1.43(m, 2H), 0.87-0.92 (m, 3H).

Example 487 Synthesis of(Z)-3-{4-[4-(3-butyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl}-2,6-dichlorophenyl}-2-methyloxyacrylicacid (B1996)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 8.25 (s, 2H), 7.96-7.99 (m, 1H), 7.73(s, 1H), 7.36-7.40 (m, 1H), 7.21-7.26 (m, 1H), 6.73 (s, 1H), 4.56 (s,2H), 3.66 (s, 3H), 3.61 (s, 3H), 3.51 (t, 2H, J=6.0 Hz), 1.51-1.60 (m,2H), 1.31-1.43 (m, 2H), 0.87-0.92 (m, 3H).

Example 488 Synthesis of(E)-3-{4-[4-(3-butyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B1997)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.96-8.00 (m, 3H), 7.75 (s, 1H),7.34-7.39 (m, 2H), 7.22-7.27 (m, 1H), 4.56 (s, 2H), 3.66 (s, 3H), 3.51(t, 2H, J=6.0 Hz), 1.81 (s, 3H), 1.51-1.60 (m, 2H), 1.31-1.43 (m, 2H),0.87-0.92 (m, 3H).

Example 489 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-heptyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1998)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 7.95-7.97 (m, 2H), 7.74 (s, 1H),7.64-7.66 (m, 1H), 7.34 (s, 1H), 7.10-7.16 (m, 1H), 7.02-7.04 (m, 1H),4.03 (t, 2H, J=6.3 Hz), 3.80 (s, 3H), 1.74-1.80 (m, 5H), 1.43-1.50 (m,2H), 1.30-1.36 (m, 6H) 0.86-0.90 (m, 3H).

Example 490 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-heptyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B1999)

1H-NMR(DMSO-d6) 12.95 (bs, 2H), 8.29 (s, 2H, 7.75 (s, 1H), 7.64-7.66 (m,1H), 7.40 (s, 1H), 7.10-7.15 (m, 1H), 7.02-7.05 (m, 1H), 4.03 (t, 2H,J=6.0 Hz), 3.80 (s, 3H), 1.76-1.81 (m, 2H), 1.69 (s, 3H), 1.45-1.50 (m,2E), 1.30-1.36 (m, 6H) 0.86-0.90 (m, 3H).

Example 491 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(3-heptyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2000)

1H-NMR(DMSO-d6) 13.56 (bs, 1H), 12.87 (bs, 1H), 7.89-7.92 (m, 2H), 7.74(s, 1H), 7.63-7.66 (m, 1H), 7.10-7.15 (m, 1H), 7.02-7.05 (m, 1H), 6.66(s, 1H), 4.03 (t, 2H, J=6.0 Hz), 3.80 (s, 3H), 3.71 (s, 3H), 1.76-1.83(m, 3H), 1.45-1.50 (m, 2H), 1.30-1.39 (m, 6H). 0.86-0.90 (m, 3H).

Example 492 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-heptyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2001)

1H-NMR(DMSO-d6) 12.90 (bs, 2H), 8.24 (s, 21), 7.74 (s, 1H), 7.63-7.66(m, 1H), 7.10-7.15 (m, 1H), 7.01-7.05 (m, 1H), 6.73 (s, 1H), 4.03 (t,2H, J=6.0 Hz), 3.80 (s, 3H), 3.61 (s, 3H), 1.76-1.83 (m, 3H), 1.45-1.50(m, 2H), 1.30-1.39 (m, 6H), 0.86-0.901 (m, 3H).

Example 493 Synthesis of(E)-3-[2,6-difluoro-4-(4-{3-[2-(4-fluorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B2002)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.95-7.88 (m, 2H), 7.85-7.88 (m, 1H),7.72 (s, 1H), 7.33 (s, 1H), 7.26-7.29 (m, 1H), 7.13-7.19 (m, 1H), 4.50(t, 1H, J=6.0 Hz), 4.34 (t, 1H, J=6.0 Hz), 3.62-3.66 (m, 5H), 3.45 (t,2H, J=6.3 Hz), 2.91 (t, 2H, J=7.0 Hz), 1.81 (s, 3H), 1.55-1.73 (m, 4H).

Example 494 Synthesis of(E)-3-[2,6-dichloro-4-(4-{3-[2-(4-fluorobutyloxy)ethyl]-2-methyloxyphenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B2003)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 8.29 (s, 2H), 7.85-7.88 (m, 1H), 7.72(s, 1H), 7.40 (s, 1H), 7.26-7.29 (m, 1H), 7.14-7.19 (m, 1H), 4.50 (t,1H, J=6.0 Hz), 4-34 (t, 1H, J=6.0 Hz), 3.62-3.66 (m, 5H), 3.45 (t, 2H,J=6.3 Hz), 2.91 (t, 2H, J=7.0 Hz), 1.55-1.73 (m, 7H).

Example 495 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-methyloxy-3-octyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2004)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.95-7.97 (m, 2H), 7.75 (s, 1H),7.64-7.66 (m, 1H), 7.34 (s, 1H), 7.10-7.15 (m, 1H), 7.02-7.04 (m, 1H),4.03 (t, 2H, J=6.3 Hz), 3.80 (s, 3H), 1.76-1.81 (m, 5H), 1.43-1.50 (m,2H), 1.28-1.36 (m, 8H). 0.86-0.90 (m, 3H).

Example 496 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-methyloxy-3-octyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2005)

1H-NMR(DMSO-d6) 12.94 (bs, 2H), 8.28 (s, 2H), 7.74 (s, 1H), 7.63-7.66(m, 1H), 7.40 (s, 1H), 7.10-7.15 (m, 1H), 7.01-7.04 (m, 1H), 4.03 (t,2H, J=6.0 Hz), 3.80 (s, 3H), 1.75-1.80 (m, 2H), 1.69 (s, 3H), 1.45-1.50(m, 2H), 1.30-1.36 (m, 8H). 0.86-0.90 (m, 3H).

Example 497 Synthesis of(E)-3-[4-(4-{3-[3-(2,2-dimethylpropyloxy)-1-methyloxypropyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methylacrylicacid (B2006)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H), 3.00-3.06 (m, 2H),1.85-1.95 (m, 2E), 1.79 (s, 3H), 0.90 (s, 9H).

Example 498 Synthesis of(E)-3-2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)-1-methyloxypropyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B2007)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.01 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.50-3.58 (m,1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H), 3.00-3.06 (m, 2H), 1.85-1.95 (m,2H), 1.69 (s, 3H), 0.90 (s, 9H).

Example 499 Synthesis of(Z)-3-[4-(4-{3-[3-(2,2-dimethylpropyloxy)-1-methyloxypropyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)-2,6-difluorophenyl]-2-methyloxyacrylicacid (B2008)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,1H, J=6.5 Hz), 3.71 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17(s, 3H), 3.00-3.06 (m, 2H), 1.85-1.95 (m, 2H), 0.90 (s, 9H).

Example 500 Synthesis of(Z)-3-[2,6-dichloro-4-(4-{3-[3-(2,2-dimethylpropyloxy)1-methyloxypropyl]-2-fluorophenyl}thiazol-2-ylcarbamoyl)phenyl]-2-methyloxyacrylicacid (B2009)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.01 (t, 1H, J=7.5 Hz),7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t, 1H, J=6.5 Hz),3.61 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 1H), 3.17 (s, 3H),3.00-3.06 (m, 2H), 1.85-1.95 (m, 2H), 0.90 (s, 9H).

Example 501 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-isopropyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2010)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz),3.50-3.58 (m, 1H), 3.35-3.42 (m, 2H), 3.17 (s, 31), 1.79-1.95 (m, 2H),1.79 (s, 3H), 1.05 (d, 6H, J=6.0 Hz).

Example 502 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-isopropyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2011)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.29 (s, 2H), 8.06 (t, 1H, J=7.5. Hz),7.64 (s, 1H), 7.30-7.40 (m, 3H), 4.72 (t, 1H, J=6.5 Hz), 3.50-3.58 (m,1H), 3.35-3.42 (m, 2H), 3.17 (s, 3H), 1.80-1.98 (m, 2H), 1.68 (s, 3H),1.05 (d, 6H, J=6.0 Hz).

Example 503 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(3-isopropyloxy-1-methyloxypropyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2012)

1H-NMR(DMSO-d6) 13.02 (s, 1H), 8.06 (t, 1H, J=7.5 Hz), 7.96 (s, 1H),7.93 (s, 1H), 7.64 (s, 1H), 7.30-7.40 (m, 2H), 6.65 (s, 1H), 4.72 (t,1H, J=6.5 Hz), 3.71 (s, 3H), 3.50-3.58 (m, 1H), 3.35-3.42 (m, 2H), 3.17(s, 3H), 1.80-1.98 (m, 2H), 1.05 (d, 6H, J=6.0 Hz).

Example 504 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methylpentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2013)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.04 (dt, 1H, J=1.8, 7.5 Hz), 7.92-8.00(m, 2H), 7.65 (d, 1H, J=2.4 Hz), 7.39-7.45 (m, 1H), 7.28-7.36 (m, 2H),4.58 (s, 2H), 3.48 (t, 2H, J=6.6 Hz), 1.81 (d, 3H, J=1.8 Hz), 1.46-1.60(m, 3H), 1.17-1.25 (m, 2H), 0.86 (d, 6H, J=6.6 Hz).

Example 505 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-3-(4-methylpentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2014)

1H-NMR(DMSO-d6) 12.97 (bs, 1H), 8.04 (dt, 1H, J=1.8, 7.5 Hz), 7.86-7.96(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.38-7.46 (m, 1H), 7.31 (t, 1H, J=7.8Hz), 6.64 (s, 1H), 4.58 (s, 2H), 3.71 (s, 3H), 3.48 (t, 2H, J=6.6 Hz),1.45-1.62 (m, 3H), 1.17-1.20 (m, 2H), 0.86 (d, 6H, J=6.6 Hz).

Example 506 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(4-methylpentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2015)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.2Hz), 7.65 (d, 1H, J=2.7 Hz), 7.38-7.46 (m, 2H), 7.31 (t, 1H, J=7.5 Hz),4.58 (s, 2H), 3.48 (t, 2H, J=6.6 Hz), 1.69 (s, 3H), 1.46-1.60 (m, 3H),1.17-1.25 (m, 2H), 0.86 (d, 6H, J=6.6 Hz).

Example 507 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(4-methylpentyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2016)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.25 (s, 2H), 8.04 (dt, 1H, J=1.5, 7.5Hz), 7.65 (d, 1H, J=2.7 Hz), 7.39-7.46 (m, 1H), 7.31 (t, 1H, J=7.8 Hz),6.73 (s, 1H), 4.58 (s, 2H), 3.61 (s, 3H), 3.48 (t, 2H, J=6.3 Hz),1.46-1.60 (m, 3H), 1.15-1.27 (m, 2H), 0.86 (d, 6H, J=6.6 Hz).

Example 508 Synthesisof(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2017)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.60-7.68 (m,2H), 7.34 (bs, 1H), 7.14-7.28 (m, 2H), 3.89 (s, 3H), 1.81 (s, 3H).

Example 509 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2018)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.68 (m, 2H), 7.40 (s,1H), 7.14-7.28 (m, 2H), 3.89 (s, 3H), 1.69 (s, 3H).

Example 510 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid. (B2019)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 8.25 (s, 2H), 7.60-7.68(m, 2H), 7.14-7.26 (m, 2H), 6.74 (s, 1H), 3.89 (s, 3H), 3.61 (s, 3H).

Example 511 Synthesis of(E)-3-(4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B2020)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H),7.39-7.41 (m, 1H), 7.25 (t, 1H, J=7-5 Hz), 6.65 (s, 1H), 4.60 (s, 2H),3.72 (s, 3H), 3.3.66 (s, 3H), 3.19 (s, 2H), 0.92 (s, 9H).

Example 512 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl)phenyl}-2-methylacrylicacid (B2021)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 8.29 (s, 2H), 7.98 (dd, 1H, J=1.5 Hz,7.5 Hz), 7.74 (s, 1H), 7.39-7.41 (m, 2H), 7.25 (t, 1H, J=7.5 Hz), 4.60(s, 2H), 3.66 (s, 3H), 3.19 (s, 2H), 1.69 (d, 3H, J=1.2 Hz), 0.92 (s,9H).

Example 513 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2,2-dimethylpropyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2022)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 8.25 (s, 2H), 7.97 (dd, 1H, J=1.5 Hz,7.5 Hz), 7.74 (s, 1H), 7.40 (dd, 1H, J=1.5 Hz, 7.5 Hz), 7.25 (t, 1H,J=7.5 Hz), 6.73 (s, 1H), 4.60 (s, 2H), 3.66 (s, 3H), 3.62 (s, 3H), 3.19(s, 2H), 0.92 (s, 9H).

Example 514 Synthesis of(E)-3-(4-{4-[3-(2-ethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B2023)

1H NMR(DMSO-d6) 12.98 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.37-7.39 (dd, 1H, J=1.8 Hz, 7.8 Hz), 7.34 (s, 1H), 7.24 (t, 1H, J=7.5Hz), 4.56 (s, 2H), 3.65 (s, 3H), 3.42 (d, 2H, J=5.7 Hz), 1.81 (s, 3H),1.26-1.51 (m, 5H), 0.85 (t, 6H, J=7.5 Hz).

Example 515 Synthesis of(Z)-3-(4-{4-[3-(2-ethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylic acid (B2024)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H),7.37-7.40 (m, 1H), 7.24 (t, 1H, J=7.5 Hz), 6.65 (s, 1E), 4.56 (s, 2H),3.72 (s, 3H), 3.65 (s, 3H), 3.42 (d, 2H, J=5.4 Hz), 1.24-1.49 (m, 5H),0.85 (t, 6H, J=7.5 Hz).

Example 516 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-ethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2025)

1H NMR(DMSO-d6) 13.00 (bs, 2H), 8.29 (s, 2H), 7.97 (dd, 1H, J=1.5 Hz,7.5 Hz), 7.74 (s, 1H), 7.37-7.41 (m, 2H), 7.25 (t, 1H, J=7.5 Hz), 4.57(s, 2H), 3.66 (s, 3H), 3.42 (d, 2H, J=5.7 Hz), 1.69 (s, 3H), 1.25-1.49(m, 5H), 0.86 (t, 6H, J=7.5 Hz).

Example 517 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-ethylbutyloxymethyl)-2-methyloxyphenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2026)

1H NMR(DMSO-d6) 12.95 (bs, 2H), 8.25 (s, 2H), 7.97 (d, 1H, J=8.1 Hz),7.73 (s, 1H), 7.38 (d, 1H, J=6.0 Hz), 7.24 (t, 1H, J=7.5 Hz), 6.73 (s,1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.62 (s, 3H), 3.42 (d, 2H, J=5.7 Hz),1.24-1.49 (m, 5H), 0.85 (t, 6H, J=7.5 Hz).

Example 518 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2027)

1H NMR(DMSO-d6) 12.94 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.34-7.40 (m, 2H), 7.24 (t, 1H, J=7.5 Hz), 4.56 (s, 2H), 3.65 (s, 3H),3.54 (t, 2H, J=6.3 Hz), 1.81 (s, 3H), 1.66-1.71 (m, 1H), 1.47 (q, 2H,6.6 Hz), 0.89 (d, 6H, J=6.6 Hz).

Example 519 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(3-methylbutyloxymethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2028)

1H NMR(DMSO-d6) 12.97 (bs, 2H), 8.29 (s, 2H), 7.97 (dd, 1H, J=9.3 Hz),7.73 (s, 1H), 7.37-7.41 (m, 2H), 7.24 (t, 1H, J=7.5 Hz), 4.56 (s, 2H),3.66 (s, 3H), 3.54 (t, 2H, J=6.6 Hz), 1.66-1.75 (m, 1H), 1.69 (s, 3H),1.47 (q, 2H, 6.6 Hz), 0.89 (d, 6H, J=6.6 Hz).

Example 520 Synthesis of(E)-3-(4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B2029)

1H-NMR(DMSO-d6) 13.04 (bs, 2H), 8.00-8.08 (m, 1H), 7.92-8.08 (m, 2H),7.65 (d, 1H, J=1.8 Hz), 7.39-7.46 (m, 1Hz), 7.28-7.36 (m, 2H), 4.58 (s,2H), 3.56 (t, 2H, J=7.2 Hz), 1.81 (s, 3H), 1.51 (t, 2H, J=7.2 Hz), 0.91(s, 9H).

Example 521 Synthesisof(Z)-3-(4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B2030)

1H-NMR(DMSO-d6) 12.99 (bs, 1H), 8.00-8.07 (m, 1H), 7.86-7.96 (m, 2H),7.65 (d, 1H, J=2.4 Hz), 7.39-7.46 (m, 1H), 7.31 (t, 1H, J=7.5 Hz), 6.65(s, 1H), 4.58 (s, 2H), 3.71 (s, 3H), 3.56 (t, 2H, J=7.2 Hz), 1.51 (t,3H, J=7.2 Hz), 0.90 (s, 9H).

Example 522 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2031)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.00-8.08 (m, 1H), 7.65(d, 1H, J=2.1 Hz), 7.39-7.48 (m, 2H), 7.31 (t, 1H, J=7.5 Hz), 4.58 (s,2H), 3.56 (t, 2H, J=7.2 Hz), 1-69 (s, 3H), 1.51 (t, 2H, J=7.2 Hz), 0.91(s, 9H).

Example 523 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(3,3-dimethylbutyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2032)

1H-NMR(DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.00-8.08 (m, 1H), 7.66(d, 111, J=2.4 Hz), 7.39-7.46 (m, 1H), 7.31 (t, 1H, J=7.5 Hz), 6.73 (s,1H), 4.59 (s, 2H), 3.62 (s, 3H), 3.56 (t, 2H, J=7.2 Hz), 1.51 (t, 2H,J=7.2 Hz), 0.91 (s, 9H).

Example 524 Synthesis of(E)-3-{4-[4-(3-cyclohexylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B2033)

1H-NMR(DMSO-d6) 13.04 (bs, 2H), 7.92-8.08 (m, 3H), 7.65 (d, 1H, J=2.4Hz), 7.39-7.46 (m, 1Hz), 7.28-7.36 (m, 2H), 4.58 (s, 2H), 1.81 (s, 3H),1.54-1.79 (m, 6H), 1.10-1.25 (m, 3H), 0.80-1.02 (m, 2H).

Example 525 Synthesis of(Z)-3-{4-[4-(3-cyclohexylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (B2034)

1H-NMR(DMSO-d6) 12.98 (bs, 1H), 8.04 (dt, 1H, J=2.1, 7.5 Hz), 7.70-7.96(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.39-7.46 (m, 1H), 7.31 (t, 1H, J=7.8Hz), 6.66 (s, 1H), 4.58 (s, 2H), 3.72 (s, 3H), 1.52-1.79 (m, 6H),1.06-1.28 (m, 3H), 0.83-1.02 (m, 2H).

Example 526 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-cyclohexylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2035)

1H-NMR (DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.04 (dt, 1H, J=1.8, 7.8Hz), 7.65 (d, 1H, J=2.4 Hz), 7.38-7.46 (m, 2H), 7.31 (t, 1H, J=7.8 Hz),4.58 (s, 2H), 1.50-1.80 (m, 6H), 1.07-1.30 (m, 3H), 0.82-1.05 (m, 2H).

Example 527 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclohexylmethyloxymethyl-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2036)

1H-NMR (DMSO-d6) 13.02 (bs, 1H), 8.25 (s, 2H), 8.00-8.08 (m, 1H), 7.65(d, 1H, J=2-4 Hz), 7.39-7.46 (m, 1H), 7.31 (t, 1H, J=8.1 Hz), 6.72 (s,1H), 4.58 (s, 2H), 3.62 (s, 3H), 1.50-1.78 (m, 6H), 1.08-1.30 (m, 3H),0.86-1.00 (m, 2H).

Example 528 Synthesis of(E)-3-(4-{4-[3-(2-ethylsufanylethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B2037)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.05 (dt, 1H, J=1.8, 7.5 Hz), 7.92-8.05(m, 2H), 7.65 (d, 1H, J=2.7 Hz), 7.42-7.48 (m, 1Hz), 7.28-7.35 (m, 2H),4.64 (s, 2H), 3.66 (t, 2H, J=6.6 Hz), 2.73 (t, 2H, J=6.9 Hz), 2.50-2.59(m, 2H), 1.81 (s, 3H), 1.17 (t, 3H, J=7.5 Hz).

Example 529 Synthesis of(Z)-3-(4-{4-[3-(2-ethylsufanylethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B2038)

1H-NMR(DMSO-d6) 12.98 (bs, 1H), 8.05 (dt, 1H, J=1.8, 7.8 Hz), 7.70-7.95(m, 2H), 7.66 (d, 1H, J=2.7 Hz), 7.42-7.49 (m, 1H), 7.32 (t, 1H, J=7.8Hz), 6.66 (s, 1H), 4.64 (s, 2H), 3.71 (s, 3H), 3.66 (t, 2H, J=6.6 Hz),2.73 (t, 2H, J=6.6 Hz), 2.50-2.59 (m, 2H), 1.17 (t, 3H, J=7.5 Hz).

Example 530 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-ethylsufanylethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2039)

1H-NMR(DMSO-d6) 13.02 (bs, 2H), 8.29 (s, 2H), 8.05 (dt, 1H, J=1.8, 7.8Hz), 7.65 (d, 1H, J=2.7 Hz), 7.42-7.48 (m, 1H), 7.40 (d, 1H, J=1.2 Hz),7.31 (t, 1H, J=7.5 Hz), 4-64 (s, 2H), 3.66 (t, 2H, J=6.6 Hz), 2.73 (t,2H, J=6.9 Hz), 2.50-2.59 (m, 2H), 1.69 (s, 3H), 1.17 (t, 3H, J=7.5 Hz).

Example 531 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[3-(2-ethylsufanylethyloxymethyl)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2040)

1H-NMR(DMSO-d6) 13.01 (bs, 1H), 8.24 (s, 2H), 8.05 (dt, 1H, J=1.8, 7.5Hz), 7.65 (d, 1H, J=2.4 Hz), 7.42-7.49 (m, 1H), 7.32 (t, 1H, J=7.5 Hz),6.73 (s, 1H), 4.64 (s, 2H), 3.66 (t, 2H, J=6.6 Hz), 3.61 (s, 3H), 2.73(t, 2H, J=6.9 Hz), 2.50-2.59 (m, 2H), 1.17 (t, 3H, J=7.5 Hz).

Example 532 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-methyloxy-3-nonyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2041)

1H-NMR(DMSO-d6) 12.92 (bs, 2H), 7.93-7.97 (m, 2H), 7.75 (s, 1H),7.63-7.66 (m, 1H), 7.34 (s, 1H), 7.08-7.15 (m, 1H), 7.02-7.04 (m, 1H),4.02 (t, 1H, J=6.3 Hz), 3.80 (s, 3H), 1.73-1.81 (m, 5H), 1.43-1.50 (m,2H), 1.26-1.38 (m, 10H), 0.84-0.88 (m, 3H).

Example 533 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-methyloxy-3-nonyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2042)

1H-NMR(DMSO-d6) 12.94 (bs, 2H), 8.28 (s, 2H), 7.74 (s, 1H), 7.63-7.66(m, 1H), 7.40 (s, 1H), 7.10-7.15 (m, 1H), 7.02-7.04 (m, 1H), 4.03 (t,1H, J=6.3 Hz), 3.80 (s, 3H), 1.73-1.81 (m, 2H), 1.69 (s, 3H), 1.43-1.50(m, 2H), 1.26-1.38 (m, 10H), 0.84-0.88 (m, 3H).

Example 534 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(4-methylpentyloxy)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2043)

1H-NMR(DMSO-d6) 12.93 (bs, 2H), 7.95-7.97 (m, 2H), 7.75 (s, 1H),7.63-7.66 (m, 1H), 7.34 (s, 1H), 7.10-7.15 (m, 1H), 7.02-7.04 (m, 1H),4.02 (t, 1H, J=6.3 Hz), 3.80 (s, 3H), 1.74-1.81 (m, 5H), 1.58-1.67 (m,1H), 1.33-1.41 (m, 2H), 0.91 (d, 6H, J=5.5 Hz).

Example 535 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(4-methylpentyloxy)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2044)

1H-NMR(DMSO-d6) 12.93 (bs, 2H), 8.28 (s, 2H), 7.74 (s, 1H), 7.63-7.66(m, 1H), 7.40 (s, 1H), 7.10-7.15 (m, 1H), 7.01-7.04 (m, 1H), 4.02 (t,1H, J=6.3 Hz), 3.80 (s, 3H), 1.74-1.82 (m, 2H), 1.69 (s, 3H), 1.58-1.67(m, 1H), 1.33-1.41 (m, 2H), 0.91 (d, 6H, J=5.5 Hz).

Example 536 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-hexyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2045)

1H-NMR(DMSO-d6) 12.96 (bs, 2H), 7.93-7.97 (m, 2H), 7.75 (s, 1H),7.63-7.66 (m, 1H), 7.34 (s, 1H), 7.10-7.15 (m, 1H), 7.01-7.04 (m, 1H),4.03 (t, 1H, J=6.3 Hz), 3.80 (s, 3H), 1.74-1.81 (m, 5H), 1.44-1.53 (m,2H), 1.32-1.37 (m, 4H), 0.87-0.92 (m, 3H).

Example 537 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-hexyloxy-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2046)

1H-NMR(DMSO-d6) 12.93 (bs, 2H), 8.27 (s, 2H), 7.72 (s, 1H), 7.62-7.64(m, 1H), 7.38 (s, 1H), 7.08-7.13 (m, 1H), 7.00-7.03 (m, 1H), 4.02 (t,1H, J=6.3 Hz), 3.78 (s, 3H), 1.72-1.81 (m, 2H), 1.67 (s, 3H), 1.42-1.51(m, 2H), 1.32-1.37 (m, 4H), 0.87-0.92 (m, 3H).

Example 538 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(1-methyloxy-4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2047)

1H-NMR(DMSO-d6) 12.97 (bs, 2H), 7.89-7.97 (m, 3H), 7.72 (s, 1H),7.24-7.34 (m, 3H), 4.53-4.57 (m, 1H), 3.61 (s, 3H), 3.16 (s, 3H), 1.81(s, 3H), 0.87-1.72 (m, 11H).

Example 539 Synthesis of(E)-3-(2,6-dichloro-4-{4-[2-methyloxy-3-(1-methyloxy-4-methylpentyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2049)

1H-NMR(DMSO-d6) 12.98 (bs, 2H), 9.29 (s, 1H), 7.89-7.92 (m, 1H), 7.72(s, 1H), 7.41 (s, 1H), 7.24-7.37 (m, 3H), 4.53-4.57 (m, 1H), 3.61 (s,3H), 3.16 (s, 3H), 0.87-1.72 (m, 14H).

Example 540 Synthesisof(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-propyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2051)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.59-7.67 (m,2H), 7.34 (bs, 1H), 7.12-7.25 (m, 2H), 4.05 (t, 2H, J=6.6 Hz), 1.74-1.84(m, 5H), 1.01 (t, 3H, J=7.2 Hz).

Example 541 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-propyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2052)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.60-7.66 (m, 2H), 7.41 (s,1H), 7.13-7.26 (m, 2H), 4.06 (t, 2H, J=6.6 Hz), 1.79 (q, 2H, J=6.9 Hz),1.70 (s, 3H), 1.02 (t, 3H, J=7.5 Hz).

Example 542 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-propyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2053)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.92 (s, 1H), 7.89 (s, 1H), 7.60-7.67 (m,2H), 7.14-7.25 (m, 2H), 6.62-6.70 (m, 1H), 4.05 (t, 2H, J=6.3 Hz), 3.71(s, 3H), 1.78 (q, 2H, J=6.3 Hz), 1.01 (t, 3H, J=7.2 Hz).

Example 543 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-propyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2054)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.25 (s, 2H), 7.59-7.66 (m, 2H),7.13-7.26 (m, 2H), 6.73 (s, 2H), 4.05 (t, 2H, J=6.6 Hz), 3.61 (s, 3H),1.78 (q, 2H, J=6.9 Hz), 1.01 (t, 3H, J=7.2 Hz).

Example 544 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-pentyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2055)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.97 (s, 1H), 7.95 (s, 1H), 7.59-7.67 (m,2H), 7.34 (bs, 1H), 7.13-7.25 (m, 2H), 4.08 (t, 2H, J=6.6 Hz), 1.72-1.89(m, 5H), 1.33-1.50 (m, 4H), 0.91 (t, 3H, J=7.2 Hz).

Example 545 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-pentyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2056)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.28 (s, 2H), 7.59-7.66 (m, 2H), 7.40(bs, 1H), 7.12-7.25 (m, 2H), 4.08 (t, 2H, J=6.6 Hz), 1.71-1.82 (m, 2H),1.69 (s, 3H), 1.30-1.51 (m, 4H), 0.91 (t, 3H, J=7.2 Hz).

Example 546 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-pentyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2057)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.93 (s, 1H), 7.89 (s, 1H), 7.59-7.65 (m,2H), 7.12-7.24 (m: 2H), 6.65 (s, 1H), 4.08 (t, 2H, J=6.6 Hz), 3.71 (s,3H), 1.71-1.80 (m, 2H), 1.35-1.50 (m, 4H), 0.91 (t, 3H, J=7.2 Hz).

Example 547 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-pentyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2058)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.24 (s, 2H), 7.58-7.65 (m, 2H),7.12-7.25 (m, 2H), 6.73 (s, 1H), 4.08 (t, 2H, J=6.6 Hz), 3.61 (s, 3H),1.72-1.82 (m, 2H), 1.33-1.48 (m, 4H), 0.91 (t, 3H, J=6.9 Hz).

Example 548 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-hexyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2059)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.59-7.66 (m,2H), 7.34 (s, 1H), 7.13-7.24 (m, 2H), 4.08 (t, 2H, J=6.6 Hz), 1.71-1.84(m, 5H), 1.30-1.51 (m, 6H), 0.89 (t, 3H, J=7.2 Hz).

Example 549 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-hexyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2060)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.65 (m, 2H), 7.41 (s,1H), 7.13-7.25 (m, 2H), 4.08 (t, 2H, J=6.6 Hz), 1.70-1.80 (m, 2H), 1.69(s, 3H), 1.30-1.50 (m, 6H), 0.89 (t, 3H, J=6.9 Hz).

Example 550 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-hexyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2061)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 7.93 (s, 1H), 7.90 (s,1H), 7.59-7.66 (m, 2H), 7.12-7.25 (m, 2H), 6.66 (s, 1H), 4.08 (t, 2H,J=6.6 Hz), 3.71 (s, 3H), 1.71-1.80 (m, 2H), 1.29-1.50 (m, 6H), 0.89 (t,3H, J=7.2 Hz).

Example 551 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-hexyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2062)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 8.25 (s, 2H), 7.59-7.66(m, 2H), 7.12-7.25 (m, 2E), 6.74 (s, 1H), 4.08 (t, 2H, J=6.6 Hz), 3.61(s, 3H), 1.70-1.81 (m, 2H), 1.30-1.50 (m, 6H), 0.89 (t, 3H, J=6.9 Hz).

Example 552 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-heptyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2063)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.59-7.66 (m,2H), 7.34 (bs, 1H), 7.13-7.25 (m, 2H), 4.08 (t, 2H, J=6.3 Hz), 1.73-1.82(m, 5H), 1.28-1.50 (m, 8H), 0.88 (t, 3H, J=7.5 Hz).

Example 553 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-heptyloxyphenyl)thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B2064)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.67 (m, 2H), 7.40 (s,1H), 7.13-7.24 (m, 2H), 4.08 (t, 2H, J=6.3 Hz), 1.70-1.80 (m, 2H), 1.69(s, 3H), 1.23-1.50 (m, 8H), 0.88 (t, 3H, J=6.9 Hz).

Example 554 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-(3-heptyloxyphenyl)thiazol-2-ylcarbamoyl)phenyl}-2-methyloxyacrylicacid (B2065)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.92 (s, 1H), 7.89 (s, 1H), 7.60-7.65 (m,2H), 7.13-7.25 (m, 2H), 6.61 (s, 1H), 4.08 (t, 2H, J=6.0 Hz), 3.72 (s,3H), 1.71-1.80 (m, 2H), 1.27-1.50 (m, 8H), 0.88 (t, 3H, J=6.9 Hz).

Example 555 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(2-fluoro-3-heptyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2066)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 8.25 (s, 2H), 7.59-7.66(m, 2H), 7.12-7.24 (m, 2H), 6.74 (s, 1H), 4.08 (t, 2H, J=6.6 Hz), 3.62(s, 3H), 1.70-1.81 (m, 2H), 1.26-1.50 (m, 8H), 0.88 (t, 3H, J=6.6 Hz).

Example 556 Synthesis of(E)-3-(2,6-difluoro-4-{4-[2-fluoro-(3-methylbutyloxy)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2067)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.60-7.67 (m,2H), 7.34 (s, 1H), 7.15-7.25 (m, 2H), 4.12 (t, 2H, J=6.6 Hz), 1.63-1.87(m, 6H), 0.96 (d, 6H, J=6.6 Hz).

Example 557 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-fluoro-(3-methylbutyloxy)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2068)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 7.93 (s, 1H), 7.90 (s,1H), 7.60-7.68 (m, 2H), 7.15-7.26 (m, 2H), 6.66 (s, 1H), 4.12 (t, 2H,J=6.6 Hz), 3.71 (s, 3H), 1.76-1.80 (m, 1H), 1.63-1.71 (m, 2H), 0.96 (d,6H, J=6.6 Hz).

Example 558 Synthesis of(Z)-3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-methylbutyloxy)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (B2069)

1H-NMR(DMSO-d6) 13.6 (bs, 1H), 13.0 (bs, 1H), 8.25 (s, 2H), 7.60-7.66(m, 2H), 7.15-7.26 (m, 2H), 6.74 (s, 1H), 4.12 (t, 2H, J=6.6 Hz), 3.62(s, 3H), 1.76-1.90 (m, 1H), 1.63-1.71 (m, 2H), 0.97 (d, 6H, J=6.6 Hz).

Example 559 Synthesis of(E)-3-(4-{4-[3-(2-cyclohexylethyloxy)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B2070)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.59-7.66 (m,2H), 7.34 (s, 1H), 7.14-7.24 (m, 2H), 4.12 (t, 2H, J=6.6 Hz), 1.41-1.83(m, 11H), 0.88-1.31 (m, 5H).

Example 560 Synthesis of(E)-3-(2,6-dichloro-4-{4-[3-(2-cyclohexylethyloxy)-2-fluorophenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2071)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.67 (m, 2H), 7.40 (s,1H), 7.14-7.25 (m, 2H), 4.12 (t, 2H, J=6.6 Hz), 1.46-1.70 (m, 1H),0.91-1.30 (m, 5H).

Example 561 Synthesis of(Z)-3-(4-{4-[3-(2-cyclohexylethyloxy)-2-fluorophenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methyloxyacrylicacid (B2072)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.92 (s, 1H), 7.89 (s, 1H), 7.59-7.66 (m,2H), 7.13-7.25 (m, 2H), 6.61 (s, 1H), 4.12 (t, 2H, J=6.6 Hz), 3.72 (s,3H), 1.46-1.80 (m, 8H,), 0.91-1.30 (m, 5H).

Example 562 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclohexylmethyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2073)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.25 (s, 2H), 7.59-7.66 (m, 2H),7.14-7.24 (m, 2H, 6.73 (s, 1H), 4.12 (t, 2H, J=6.6 Hz), 3.61 (s, 3H),1.46-1.71 (m, 8H), 0.95-1.30 (m, 5H).

Example 563 Synthesis of(E)-3-{4-[4-(3-cyclohexylmethyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B2074)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.98 (s, 1H), 7.95 (s, 1H), 7.59-7.66 (m,2H) 7.34 (s, 1H), 7.12-7.24 (m, 2H), 3.90 (d, 2H, J=5.7 Hz), 1.61-1.89(m, 9H), 1.03-1.55 (m, 5H).

Example 564 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-cyclohexylmethyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2075)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.66 (m, 2H), 7.41 (s,1H), 7.12-7.24 (m, 2H), 3.90 (d, 2H, J=6.0 Hz), 1.62-1.88 (m, 9H),1.02-1.37 (m, 5H).

Example 565 Synthesis of(Z)-3-{4-[4-(3-cyclohexylmethyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (B2076)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.93 (s, 1H), 7.90 (s, 1H), 7.60-7.67 (m,2H), 7.12-7.25 (m, 2H), 6.66 (s, 1H), 3.90 (d, 2H, J=5.4 Hz), 3.71 (s,3H), 1.62-1.89 (m, 6H), 1.02-1.37 (m, 5H).

Example 566 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclohexylmethyloxy-2-fluorophenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2077)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.25 (s, 2H), 7.59-7.66 (m, 2H),7.13-7.24 (m, 2H), 6.73 (s, 1H), 3.90 (d, 2H, J=5.7 Hz), 3.61 (s, 3H),1.62-1.89 (m, 6H), 1.03-1.35 (m, 5H).

Example 567 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-isobutyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2078)

1H NMR(DMSO-d6) 13.01 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H),7.38-7.41 (m, 1H), 7.34 (s, 1H), 7.25 (t, 1H, J=7.5 Hz), 4.57 (s, 2H),3.66 (s, 3H), 3.29 (d, 2H, J=6.9 Hz), 1.81-1.91 (m, 1H), 1.81 (s, 3H),0.91 (d, 6H, J=6.6 Hz).

Example 568 Synthesis of(E)-3-{2,6-difluoro-4-[4-(3-isobutyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2079)

1H NMR(DMSO-d6) 12.92 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H), 7.39(d, 1H, J=7.5 Hz), 7.25 (t, 1H, J=7.5 Hz), 6.65 (s, 1H), 4.57 (s, 2H),3.72 (s, 3H), 3.65 (s, 3H), 3.29 (d, 2H, J=6.6 Hz), 1.83-1.91 (m, 1H),0.91 (d, 6H, J=6.6 Hz).

Example 569 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-isobutyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2080)

1H NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.96-7.99 (m, 1H), 7.74(s, 1H), 7.38-7.41 (m, 2H), 7.25 (t, 1H, J=7.5 Hz), 4.57 (s, 2H), 3.66(s, 3H), 3.29 (d, 2H, J=6.6 Hz), 1.83-1.92 (m, 1H), 1.69 (s, 3H), 0.91(d, 6H, J=6.6 Hz).

Example 570 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-isobutyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2081)

1H NMR(DMSO-d6) 12.97 (bs, 2H), 8.25 (s, 2H), 7.97 (dd, 1H, J=1.5 Hz,7.8 Hz), 7.74 (s, 1H), 7.39 (dd, 1H, J=1.5 Hz, 7.5 Hz), 7.25 (t, 1H,J=7.8 Hz), 6.72 (s, 1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.62 (s, 3H), 3.29(d, 2H, J=6.6 Hz), 1.83-1.92 (m, 1H), 0.91 (d, 6H, J=6.6 Hz).

Example 571 Synthesis of(E)-3-{4-[4-(3-cylohexylmethyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B2082)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.95-7.99 (m, 3H), 7.74 (s, 1H), 7.39(dd, 1H, J=1.8 Hz, 7.5 Hz), 7.34 (s, 1H), 7.24 (t, 1H, J=7.5 Hz), 4.57(s, 2H), 3.66 (s, 3H), 3.39 (d, 2H, J=6.9 Hz), 2.12-2.21 (m, 1H), 1.81(s, 3H), 1.65-1.73 (m, 2H), 1.47-1.58 (m, 4H), 1.21-1.27 (m, 2H).

Example 572 Synthesis of(Z)-3-{4-[4-(3-cyclohexylmethyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methyloxyacrylicacid (B2083)

1H NMR(DMSO-d6) 12.93 (bs, 2H), 7.90-7.99 (m, 3H), 7.74 (s, 1H), 7.39(dd, 1H, J=1.8 Hz, 7.5 Hz), 7.24 (t, 1H, J=7.5 Hz), 6.65 (s, 1H), 4.57(s, 2H), 3.72 (s, 3H), 3.66 (s, 3H), 3.39 (d, 2H, J=6.9 Hz), 2.11-2.21(m, 1H), 1.66-1.73 (m, 2H), 1.47-1.58 (m, 4H), 1.23-1.30 (m, 2H).

Example 573 Synthesis of(E)-3-{2,6-dichloro-4-[4-(3-cyclopentylmethyloxymethyl-2-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2084)

1H NMR(DMSO-d6) 12.99 (bs, 2H), 8.29 (s, 2H), 7.97 (dd, 1H, J=1.8 Hz,7.8 Hz), 7.73 (s, 1H), 7.38-7.41 (m, 2H), 7.24 (t, 1H, J=7.5 Hz), 4.57(s, 2H), 3.66 (s, 3H), 3.39 (d, 2H, J=7.2 Hz), 2.11-2.19 (m, 1H), 1.69(s, 3H), 165-1.73 (m, 2H), 1.49-1.58 (m, 4H), 1.21-1.27 (m, 2H).

Example 574 Synthesis of(Z)-3-{2,6-dichloro-4-[4-(3-cyclopentylmethyloxymethyl-2-methylphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2085)

1H NMR(DMSO-d6) 12.95 (bs, 2H), 8.25 (s, 2H), 7.97 (dd, 1H, J=1.8 Hz,7.8 Hz), 7.73 (s, 1H), 7.39 (dd, 1H, J=1.8 Hz, 7.5 Hz), 7.24 (t, 1H,J=7.8 Hz), 6.73 (s, 1H), 4.57 (s, 2H), 3.66 (s, 3H), 3.62 (s, 3H), 3.39(d, 2H, J=7.2 Hz), 2.11-2.21 (m, 1H), 1.65-1.71 (m, 2H), 1.51-1.58 (m,4H), 1.21-1.27 (m, 2H).

Example 575 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-isobutyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2086)

1H NMR(DMSO-d6) 12.85 (bs, 2H), 7.79 (d, 2H, J=8.4 Hz), 7.43-7.48 (m,2H), 7.16 (s, 1H), 6.96-7.07 (m, 2H), 3.70 (d, 2H, J=6.6 Hz), 1.86-1.92(m, 1H), 1.63 (s, 3H), 0.84 (d, 6H, J=6.6 Hz).

Example 576 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-isobutyloxyphenyl)thiazol-2-ylcarbamoyl}phenyl)-2-methylacrylicacid (B2087)

1H NMR(DMSO-d6) 12.77 (bs, 2H), 8.11 (s, 2H), 7.43-7.48 (m, 2H), 7.23(d, 1H, J=1.2 Hz), 6.98-7.07 (m, 2H), 3.70 (d, 2H, J=6.3 Hz), 1.86-1.95(m, 1H), 1.52 (s, 3H), 0.84 (d, 6H, J=6.6 Hz).

Example 577 Synthesis of(E)-3-{2,6-difluoro-4-[4-(2-fluoro-3-(2-methylbutyloxyphenyl)thiazol-2-ylcarbamoyl)phenyl]-2-methylacrylicacid (B2088)

1H NMR(DMSO-d6) 12.84 (bs, 2H), 7.79 (d, 2H, J=8.4 Hz), 7.43-7.48 (m,2H), 7.16 (s, 1H), 6.97-7.07 (m, 2H), 3.68-3.81 (m, 2H), 1.68-1.73 (m,1H), 1.64 (s, 3H), 1.34-1.41 (m, 1H), 1.05-1.14 (m, 1H), 0.83 (d, 3H,J=6.6 Hz), 0.76 (t, 3H, J=7.5 Hz).

Example 578(E)-3-{4-[6-(3,3-dimethylbutyn-lyl)-4,5-dihydronaphtho[1,2-d]thiazol-2-ylcarbamoyl]-2,6-difluorophenyl}-2-methylacrylicacid (B2089)

1H-NMR(DMSO-d6) 12.87 (bs, 2H), 7.93-7.96 (m, 2H), 7.69-7.72 (m, 1H),7.32 (s 1H), 7.22-7.29 (m, 2H), 3.13-3.18 (m, 2H), 2.99-3.04 (m, 2H),1.33 (s, 9H).

Example 579 Synthesis of(Z)-3-(2,6-difluoro-4-{4-[2-methyloxy-3-(2-propyloxyethyl)phenyl]thiazol-2-ylcarbamoyl}phenyl)-2-methyloxyacrylicacid (132090)

1H-NMR(DMSO-d6) 13.57 (bs, 1H), 12.93 (bs, 1H), 7.86-7.92 (m, 3H), 7.72(s, 1H), 7.27-7.30 (m, 1H), 7.14-7.19 (m, 1H), 6.66 (s, 1H), 3.71 (s,3H), 3.60-3.65 (m, 5H), 3.70 (t, 2H, J=6.6 Hz), 2.91 (t, 2H, J=6.9 Hz),1.47-1.54 (m, 2H), 0.85 (t, 3H, J=7.5 Hz).

Example 580 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-(3-methylbutyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylic acid (B2097)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 8.29 (s, 2H), 7.59-7.66 (m, 2H), 7.40 (s,1H), 7.15-7.25 (m, 2H), 4.11 (t, 2H, J=6.6 Hz), 1.76-1.87 (m, 1H),1.63-1.72 (m, 5H), 0.96 (d, 6H, J=6.6 Hz).

Example 581 Synthesis of(E)-3-{2,6-dichloro-4-[4-(2-fluoro-3-(2-methylbutyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methylacrylicacid (B2098)

1H NMR(DMSO-d6) 12.82 (bs, 2H), 8.12 (s, 2H), 7.43-7.48 (m, 2H), 7.23(s, 1H), 6.96-7.07 (m, 2H), 3.68-3.81 (m, 2H), 1.68-1.70 (m, 1H), 1.52(s, 3H), 1.36-1.43 (m, 1H), 1.07-1.14 (m, 1H), 0.83 (d, 3H, J=6.9 Hz),0.76 (t, 3H, J=6.9 Hz).

Example 582(E)-3-(4-{4-[2-ethyloxy-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbamoyl}-2,6-difluorophenyl)-2-methylacrylicacid (B2099)

1H-NMR(DMSO-d6) 13.00 (bs, 2H), 7.93-8.00 (m, 2H), 7.86 (dd, 1H, J=2.1,7.8 Hz), 7.70 (s, 1H), 7.34 (s, 1H), 7.31 (dd, 3H, J=2.1, 7.5 Hz), 7.25(t, 1H, J=7.5 Hz), 4.53-4.57 (m, 1H), 3.66-3.74 (m, 2H), 3.15 (s, 3H),1.81 (s, 3H), 1.52-1.78 (m, 2H), 1.18-1.50 (m, 17H), 0.83-0.87 (m, 3H).

Example 583 Synthesis of(Z)-3-{2,6-difluoro-4-[4-(2-fluoro-3-methyloxyphenyl)thiazol-2-ylcarbamoyl]phenyl}-2-methyloxyacrylicacid (B2100)

1H-NMR(DMSO-d6) 13.0 (bs, 2H), 7.92 (s, 1H), 7.90 (s, 1H), 7.60-7.67 (m,2H), 7.13-7.28 (m, 2H), 6.66 (s, 1H), 3.89 (s, 3H), 3.71 (s, 3H).

The following compounds can be synthesized by similar reaction toabove-mentioned method.

wherein R⁶, R⁷, and R⁸ are each independently fluoro, chloro, or methyl;

R¹ is fluoro or methyl;

R¹ is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl,n-pentyl, neopentyl, n-hexyl, isohexyl, 3,3-dimethylbutyl,1-methyloxyethyl, 1-dimethyloxypropyl, 1-methyloxy-3-n-propyloxypropyl,1-methyloxy-3-n-hexyloxypropyl, 1-methyloxybutyl,1-methyloxy-4-n-pentyloxypropyl, 1-methyloxy-2-methylpropyl,1-methyloxypentyl, 1-methyloxy-3-methylbutyl, 3-methyloxy-3-methylbutyl,1-methyloxy-2,2-dimethylpropyl, 1-methyloxyhexyl, 4-methyloxyhexyl,1-methyloxy-4-methylpentyl, 1-methyloxy-3,3-dimethylbutyl,1-methyloxyheptyl, 4-methyloxy-4-heptyl,3-methyloxy-2,4-dimethyl-3-pentyl, 1-methyloxyoctyl, 3-methyloxyoctyl,1-methyloxynonyl, 1-methyloxydecyl, 3-methyloxydecyl,1-methyloxyundecyl, 1-methyloxydoecyl, 1-methyloxy-1-cyclohexylmethyl,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl, 1-ethyloxyethyl,1-ethyloxypropyl, 1-ethyloxy-3-n-hexyloxypropyl,1-(4-ethyloxybutyloxy)propyl, 1-ethyloxybutyl,1-ethyloxy-4-n-pentyloxybutyl, 1-ethyloxy-2-methylproyl,1-ethyloxypentyl, 1-ethyloxy-3-methylbutyl,1-ethyloxy-2,2-dimethylpropyl, 1-ethyloxyhexyl,1-ethyloxy-3,3-dimethylbutyl, 1-ethyloxyheptyl, 1-ethyloxyoctyl,1-ethyloxynonyl, 1-ethyloxydecyl, 1-ethyloxyundecyl, 1-ethyloxydodecyl,1-ethyloxy-1-cyclohexylmethyl, 1-n-propyloxyethyl, 1-n-propyloxypropyl,3-n-propyloxypropyl, 1-n-propyloxy-3-n-hexyloxypropyl,1-n-propyloxybutyl, 1-n-propyloxy-4-n-pentyloxybutyl,1-n-propyloxy-2-methylpropyl, 1-n-propyloxypentyl,1-n-propyloxy-3-methylbutyl, 1-n-propyloxy-2,2-dimethylpropyl,1-n-propyloxyhexyl, 1-n-propyloxy-3,3-dimethylbutyl,1-n-propyloxyheptyl, 1-n-propyloxyoctyl, 1-n-propyloxynonyl,1-n-propyloxydecyl, 1-n-propyloxyundecyl, 1-n-propyloxydodecyl,1-n-propyloxy-1-cyclohexylmethyl, 1-isopropyloxyethyl,1-isopropyloxypropyl, 3-isopropyloxypropyl,1-isopropyloxy-3-n-hexyloxypropyl, 1-isopropyloxybutyl,1-iso-propyloxy-4-n-pentyloxybutyl, 1-isopropyloxy-2-methylpropyl,1-isopropyloxypentyl, 1-isopropyloxy-3-methylbutyl,1-isopropyloxy-2,2-dimethylpropyl, 1-isopropyloxyhexyl,1-isopropyloxy-3,3-dimethylbutyl, 1-isopropyloxyheptyl,1-isopropyloxyoctyl, 1-isopropyloxynonyl, 1-isopropyloxydecyl,1-isopropyloxyundecyl, 1-isopropyloxydodecyl,1-isopropyloxy-1-cyclohexylmethyl, 1-n-butyloxyethyl,1-n-butyloxypropyl, 3-n-butyloxypropyl, 1-n-butyloxybutyl,1,4-di(n-butyloxy)butyl, 1-n-butyloxy-2-methylpropyl,1-n-butyloxypentyl, 1-n-butyloxy-3-methylbutyl,1-n-butyloxy-2,2-dimethylpropyl, 1-n-butyloxyhexyl,1-n-butyloxy-3,3-dimethylbutyl, 1-n-butyloxyheptyl, 1-n-butyloxyoctyl,1-n-butylxynonyl, 1-n-butyloxydecyl, 1-n-butyloxyundecyl,1-n-butyloxydodecyl, 1-n-butyloxy-1-cyclohexylmethyl,1-isobutyloxyethyl, 1-isobutyloxypropyl, 1-isobutyloxybutyl,1-isobutyloxy-2-methylpropyl, 1-isobutyloxypentyl,1-isobutyloxy-3-methylbutyl, 1-isobutyloxy-2,2-dimethylpropyl,1-isobutyloxyhexyl, 1-isobutyloxy-3,3-dimethbylbutyl,1-isobutyloxyheptyl, 1-isobutyloxyoctyl, 1-isobutylxynonyl,1-isobutyloxydecyl, 1-isobutyloxyundecyl, 1-isobutyloxydodecyl,1-isobutyloxy-1-eyclohexylmethyl, 1-t-butyloxyethyl, 1-t-butyloxypropyl,1-t-butyloxybutyl, 1-t-butyloxy-2-methylpropyl, 1-t-butyloxypentyl,1-t-butyloxy-3-methylbutyl, 1-t-butyloxy-2,2-dimethylpropyl,1-t-butyloxyhexyl, 1-t-butyloxy-3,3-dimethylbutyl, 1-t-butyloxyheptyl,1-t-butyloxyoctyl, 1-t-butyloxynonyl, 1-t-butyloxydecyl,1-t-butyloxyundecyl, 1-t-butyloxydodecyl,1-t-butyloxy-1-cyclohexylmethyl, n-pentyloxymethyl, 1-n-pentyloxyethyl,1-n-pentyloxypropyl, 3-n-pentyloxypropyl,1-n-pentyloxy-3-methylthiopropyl, 1-n-pentyloxybutyl,1-n-pentyloxy-2-methylpropyl, 1-n-pentyloxypentyl,1-n-pentyloxy-3-methylbutyl, 1-n-pentyloxy-2,2-dimethylpropyl,1-n-pentyloxyhexyl, 1-n-pentyloxy-3,3-dimethylbutyl,1-n-pentyloxyheptyl, 1-n-pentyloxyoctyl, 1-n-pentyloxynonyl,1-n-pentyloxydecyl, 1-n-pentyloxyundecyl, 1-n-pentyloxydodecyl,1-n-pentyloxy-1-cyclohexylmethyl, 1-neopentyloxyethyl,1-neopentyloxypropyl, 3-neopentyloxypropyl,1-neopentyloxy-3-methylthiopropyl, 1-neopenltyloxybutyl,1-neopentyloxy-2-methylpropyl, 1-neopentyloxypentyl,1-neopentyloxy-3-methylbutyl, 1-neopentyloxy-2,2-dimethylpropyl,1-neopentyloxyhexyl, 1-neopentyloxy-3,3-dimethylbutyl,1-neopentyloxyheptyl, 1-neopentyloxyoctyl, 1-neopentyloxynonyl,1-neopentyloxydecyl, 1-neopentyloxyundecyl, 1-neopentyloxydodecyl,1-neopentyloxy-1-cyclohexylmethyl, 1-n-hexyloxyethyl,1-n-hexyloxypropyl, 3-n-hexyloxypropyl, 1-n-hexyloxy-3-methylthiopropyl,1-n-hexyloxybutyl, 1-n-hexyloxy-2-methylpropyl, 1-n-hexyloxypentyl,1-n-hexyloxy-3-methylbutyl, 1-n-hexyloxy-2,2-dimethylpropyl,1-n-hexyloxyhexyl, 1-n-hexyloxy-3,3-dimethylbutyl, 1-n-hexyloxyheptyl,1-n-hexyloxyoctyl, 1-n-hexyloxynonyl, 1-n-hexyloxydecyl,1-n-hexyloxyundecyl, 1-n-hexyloxydodecyl,1-n-hexyloxy-1-cyclohexylmethyl, 3-isohexyloxypropyl,3-(2-ethylbutyloxy)propyl, 3-(3,3-dimethylbutyloxy)propyl,3-(2-cyclopentylethyloxy)propyl, 1-n-octyloxyethyl, orn-dodecyloxymethyl

(Compound No., R⁶, R⁷, R⁸, R¹, R²)=(B102, F, F, Me, F, methyl), (B103,F, F, Me, F, ethyl), (B104, F, F, Me, F, n-propyl), (B105, F, F, Me, F,isopropyl), (B106, F, F, Me, F, n-butyl), (B107, F, F, Me, F, isobutyl),(B108, F, F, Me, F, t-butyl), (B109, F, F, Me, F, neopentyl), (B110, F,F, Me, F, n-hexyl), (B111, F, F, OMe, F, methyl), (B112, F, F, OMe, F,ethyl), (B113, F, F, OMe, F, n-propyl), (B114, F, F, OMe, F, isopropyl),(B115, F, F, OMe, F, n-butyl), (B116, F, F, OMe, F, isobutyl), (B117, F,F, OMe, F, t-butyl), (B118, F, F, OMe, F, n-pentyl), (B119, F, F, OMe,F, neopentyl), (B112, F, F, OMe, F, n-hexyl), (B123, F, F, Me, OMe,methyl), (B124, F, F, Me, OMe, ethyl), (B125, F, F, Me, OMe, n-propyl),(B126, F, F, Me, OMe, isopropyl), (B127, F, F, Me, OMe, n-butyl), (B128,F, F, Me, OMe, isobutyl), (B129, F, F, Me, OMe, t-butyl), (B130, F, F,Me, OMe, n-pentyl), (B131, F, F, Me, OMe, neopentyl), (B132, F, F, Me,OMe, n-hexyl), (B133, F, F, Me, OMe, isohexyl), (B135, F, F, OMe, OMe,methyl), (B136, F, F, OMe, OMe, ethyl), (B137, F, F, OMe, OMe,n-propyl), (B138, F, F, OMe, OMe, isopropyl), (B139, F, F, OMe, OMe,n-butyl), (B140, F, F, OMe, OMe, isobutyl), (B141, F, F, OMe, OMe,t-butyl), (B142, F, F, OMe, OMe, n-pentyl), (B143, F, F, OMe, OMe,neopentyl), (B144, F, F, OMe, OMe, n-hexyl), (B145, F, F, OMe, OMe,isohexyl), (B146, F, F, OMe, OMe, 3,3-dimethylbutyl), (B147, Cl, Cl, Me,F, methyl), (B148, Cl, Cl, Me, F, ethyl), (B149, Cl, Cl, Me, F,n-propyl), (B150, Cl, Cl, Me, F, isopropyl), (B151, Cl, Cl, Me, F,n-butyl), (B152, Cl, Cl, Me, F, isobutyl), (B153, Cl, Cl, Me, F,t-butyl), (B154, Cl, Cl, Me, F, n-pentyl), (B155, Cl, Cl, Me, F,neopentyl), (B156, Cl, Cl, Me, F, n-hexyl), (B157, Cl, Cl, Me, F,isohexyl), (B158, Cl, Cl, Me, F, 3,3-dimethylbutyl), (B159, Cl, Cl, OMe,F, methyl), (B160, Cl, Cl, OMe, F, ethyl), (B161, Cl, Cl, OMe, F,n-propyl), (B162, Cl, Cl, OMe, F, isopropyl), (B163, Cl, Cl, OMe, F,n-butyl), (B164, Cl, Cl, OMe, F, isobutyl), (B165, Cl, Cl, OMe, F,t-butyl), (B166, Cl, Cl, OMe, F, n-pentyl), (B167, Cl, Cl, OMe, F,neopentyl), (B168, Cl, Cl, OMe, F, n-hexyl), (B171, Cl, Cl, Me, OMe,methyl), (B172, Cl, Cl, Me, OMe, ethyl), (B173, Cl, Cl, Me, OMe,n-propyl), (B174, Cl, Cl, Me, OMe, isopropyl), (B175, Cl, Cl, Me, OMe,n-butyl), (B176, Cl, Cl, Me, OMe, isobutyl), (B177, Cl, Cl, Me, OMe,t-butyl), (B178, Cl, Cl, Me, OMe, n-pentyl), (B179, Cl, Cl, Me, OMe,neopentyl), (B180, Cl, Cl, Me, OMe, n-hexyl), (B181, Cl, Cl, Me, OMe,isohexyl), (B182, Cl, Cl, Me, OMe, 3,3-dimethylbutyl), (B183, Cl, Cl,OMe, OMe, methyl), (B184, Cl, Cl, OMe, OMe, ethyl), (B185, Cl, Cl, OMe,OMe, n-propyl), (B186, Cl, Cl, OMe, OMe, isopropyl), (B187, CG, Cl, OMe,OMe, n-butyl), (B188, Cl, Cl, OMe, OMe, isobutyl), (B189, Cl, Cl, OMe,OMe, t-butyl), (B190, Cl, Cl, OMe, OMe, n-pentyl), (B191, Cl, Cl, OMe,OMe, neopentyl), (B192, Cl, Cl, OMe, OMe, n-hexyl), (B193, Cl, Cl, OMe,OMe, isohexyl), (B194, Cl, Cl, OMe, OMe, 3,3-dimethylbutyl), (B196, F,F, Me, F, 1-methyloxypropyl), (B197, F, F, Me, F, 1-methyloxybutyl),(B198, F, F, Me, F, 1-methyloxy-2-methylpropyl), (B199, F, F, Me, F,1-methyloxypentyl), (B200, F, F, Me, F, 1-methyloxy-3-methylbutyl),(B201, F, F, Me, F, 3-methyloxyoctyl), (B202, F, F, Me, F,1-ethyloxyethyl), (B203, F, F, Me, F, 1-ethyloxy-3-n-hexyloxypropyl),(B204, F, F, Me, F, 1-ethyloxy-4-n-pentyloxybutyl), (B205, F, F, Me, F,1-ethyloxybutyl), (B206, F, F, Me, F, 1-ethyloxy-2-methylpropyl), (B207,F, F, Me, F, 1-ethyloxy-3-methylbutyl), (B208, F, F, Me, F,1-ethyloxyhexyl), (B209, F, F, Me, F, 1-ethyloxy-3,3-dimethylbutyl),(B210, F, F, Me, F, 1-ethyloxyheptyl), (B211, F, F, Me, F,1-ethyloxyoctyl), (B212, F, F, Me, F, 1-ethyloxynonyl), (B213, F, F, Me,F, 1-ethyloxydecyl), (B214, F, F, Me, F, 1-ethyloxyundecyl), (B215, F,F, Me, F, 1-ethyloxydodecyl), (B217, F, F, Me, F, 1-n-propyloxypropyl),(B218, F, F, Me, F, 3-n-propyloxypropyl), (B219, F, F, Me, F,1-n-propyloxy-3-n-hexyloxypropyl), (B220, F, F, Me, F,1-n-propyloxy-4-n-pentyloxybutyl), (B221, F, F, Me, F,1,4-di(n-propyloxy)butyl), (B222, F, F, Me, F,1-n-propyloxy-2-methylpropyl), (B223, F, F, Me, F,1-n-propyloxy-3-methylbutyl), (B224, F, F, Me, F,1-n-propyloxy-2,2-dimethylpropyl), (B225, F, F, Me, F,1-n-propyloxyhexyl), (B226, F, F, Me, F,1-n-propyloxy-3,3-dimethylbutyl), (B227, F, F, Me, F,1-n-propyloxyheptyl), (B228, F, F, Me, F, 1-n-propyloxyoctyl), (B229, F,F, Me, F, 1-n-propyloxynonyl), (B230, F, F, Me, F, 1-n-propyloxydecyl),(B231, F, F, Me, F, 1-n-propyloxyundecyl), (B232, F, F, Me, F,1-n-propyloxydodecyl), (B234, F, F, Me, F, 1-isopropyloxyethyl), (B235,F, F, Me, F, 1-isopropyloxypropyl), (B236, F, F, Me, F,3-isopropyloxypropyl), (B237, F, F, Me, F,1-isopropyloxy-3-n-hexyloxypropyl), (B238, F, F, Me, F,1-isopropyloxybutyl), (B239, F, F, Me, F,1-isopropyloxy-4-n-pentyloxybutyl), (B240, F, F, Me, F,1-isopropyloxy-2-methylpropyl), (B241, F, F, Me, F,1-isopropyloxypentyl), (B242, F, F, Me, F,1-isopropyloxy-3-methylbutyl), (B243, F, F, Me, F,1-isopropyloxy-2,2-dimethylpropyl), (B244, F, F, Me, F,1-isopropyloxyhexyl), (B245, F, F, Me, F,1-isopropyloxy-3,3-dimethylbutyl), (B246, F, F, Me, F,1-isopropyloxyheptyl), (B247, F, F, Me, F, 1-isopropyloxyoctyl), (B248,F, F, Me, F, 1-isopropyloxynonyl), (B249, F, F, Me, F,1-isopropyloxydecyl), (B250, F, F, Me, F, 1-isopropyloxyundecyl), (B251,F, F, Me, F, 1-isopropyloxydodecyl), (B252, F, F, Me, F,1-isopropyloxy-1-cyclohexylmethyl), (B253, F, F, Me, F,1-n-butyloxy-2-methylpropyl), (B254, F, F, Me, F,1-n-butyloxy-3-methylbutyl), (B256, F, F, Me, F, 1-n-butyloxyhexyl),(B257, F, F, Me, F, 1-n-butyloxy-3,3-dimethylbutyl), (B258, F, F, Me, F,1-n-butyloxyheptyl), (B259, F, F, Me, F, 1-n-butyloxyoctyl), (B260, F,F, Me, F, 1-n-butyloxynonyl), (B261, F, F, Me, F, 1-n-butyloxydecyl),(B262, F, F, Me, F, 1-n-butyloxyundecyl), (B263, F, F, Me, F,1-n-butyloxydodecyl), (B165, F, F, Me, F, 1-isobutyloxyethyl), (B266, F,F, Me, F, 1-isobutyloxypropyl), (B267, F, F, Me, F, 1-isobutyloxybutyl),(B268, F, F, Me, F, 1-isobutyloxy-2-methylpropyl), (B269, F, F, Me, F,1-isobutyloxypentyl), (B270, F, F, Me, F, 1-isobutyloxy-3-methylbutyl),(B271, F, F, Me, F, 1-isobutyloxy-2,2-dimethylpropyl), (B272, F, F, Me,F, 1-isobutyloxyhexyl), (B273, F, F, Me, F,1-isobutyloxy-3,3-dimethylbutyl), (B274, F, F, Me, F,1-isobutyloxyheptyl), (B275, F, F, Me, F, 1-isobutyloxyoctyl), (B276, F,F, Me, F, 1-isobutyloxyynonyl), (B277, F, F, Me, F, 1-isobutyloxydecyl),(B278, F, F, Me, F, 1-isobutyloxyundecyl), (B279, F, F, Me, F,1-isobutyloxydodecyl), (B280, F, F, Me, F,1-isobutyloxy-1-cyclohexylmethyl), (B3281, F, F, Me, F,1-t-butyloxyethyl), (B282, F, F, Me, F, 1-t-butyloxypropyl), (B283, F,F, Me, F, 1-t-butyloxybutyl), (B284, F, F, Me, F,1-t-butyloxy-2-methylpropyl), (B285, F, F, Me, F, 1-t-butyloxypentyl),(B286, F, F, Me, F, 1-t-butyloxy-3-methylbutyl), (B287, F, F, Me, F,1-t-butyloxy-2,2-dimethylpropyl), (B288, F, F, Me, F,1-t-butyloxyhexyl), (B289, F, F, Me, F, 1-t-butyloxy-3,3-dimethylbutyl),(B290, F, F, Me, F, 1-t-butyloxyheptyl), (B291, F, F, Me, F,1-t-butyloxyoctyl), (B292, F, F, Me, F, 1-t-butyloxynonyl), (B293, F, F,Me, F, 1-t-butyloxydecyl), (B294, F, F, Me, F, 1-t-butyloxyundecyl),(B295, F, F, Me, F, 1-t-butyloxyydodecyl), (B296, F, F, Me, F,1-t-butyloxy-1-cyclohexylmethyl), (B297, F, F, Me, F,1-n-pentyloxy-2-methylpropyl), (B298, F, F, Me, F,1-n-pentyloxy-3-methylbutyl), (B299, F, F, Me, F, 1-n-pentyloxyhexyl),(B300, F, F, Me, F, 1-n-pentyloxy-3,3-dimethylbutyl), (B301, F, F, Me,F, 1-n-pentyloxyheptyl), (B302, F, F, Me, F, 1-n-pentyloxyoctyl), (B303,F, F, Me, F, 1-n-pentyloxynonyl), (B304, F, F, Me, F,1-n-pentyloxydecyl), (B305, F, F, Me, F, 1-n-pentyloxyundecyl), (B306,F, F, Me, F, 1-n-pentyloxydodecyl), (B307, F, F, Me, F,1-neopentyloxyethyl), (B308, F, F, Me, F, 1-neopentyloxypropyl), (B309,F, F, Me, F, 1-neopentyloxybutyl), (B310, F, F, Me, F,1-neopentyloxy-2-methylpropyl), (B311, F, F, Me, F,1-neopentyloxypentyl), (B312, F, F, Me, F,1-neopentyloxy-3-methylbutyl), (B313, F, F, Me, F,1-neopentyloxy-2,2-dimethylpropyl), (B314, F, F, Me, F,1-neopentyloxyhexyl), (B315, F, F, Me, F,1-neopentyloxy-3,3-dimethylbutyl), (B316, F, F, Me, F,1-neopentyloxyheptyl), (B317, F, F, Me, F, 1-neopentyloxyoctyl), (B318,F, F, Me, F, 1-neopentyloxynonyl), (B319, F, F, Me, F,1-neopentyloxydecyl), (B320, F, F, Me, F, 1-neopentyloxyundecyl), (B321,F, F, Me, F, 1-neopentyloxydodecyl), (B322, F, F, Me, F,1-neopentyloxy-1-cyclohexylmethyl), (B323, F, F, Me, F,1-n-hexyloxyethyl), (B324, F, F, Me, F, 1-n-hexyloxybutyl), (B3325, F,F, Me, F, 1-n-hexyloxy-2-methylpropyl), (B326, F, F, Me, F,1-n-hexyloxypentyl), (B327, F, F, Me, F, 1-n-hexyloxy-3-methylbutyl),(B328, F, F, Me, F, 1-n-hexyloxy-2,2-dimethylpropyl), (B329, F, F, Me,F, 1-n-hexyloxyhexyl), (B330, F, F, Me, F,1-n-hexyloxy-3,3-dimethylbutyl), (B331, F, F, Me, F,1-n-hexyloxyheptyl), (B332, F, F, Me, F, 1-n-hexyloxyoctyl), (B333, F,F, Me, F, 1-n-hexyloxynonyl), (B334, F, F, Me, F, 1-n-hexyloxydecyl),(B335, F, F, Me, F, 1-n-hexyloxyundecyl), (B336, F, F, Me, F,1-n-hexyloxydodecyl), (B337, F, F, Me, F,1-n-hexyloxy-1-cyclohexylmethyl), (B338, F, F, Me, OMe,1-methyloxyethyl), (B339, F, F, Me, OMe, 1-methyloxypropyl), (B340, F,F, Me, OMe, 1-methyloxy-3-n-hexyloxypropyl), (B341, F, F, Me, OMe,1-methyloxybutyl), (B342, F, F, Me, OMe,1-methyloxy-4-n-pentyloxybutyl), (B343, F, F, Me, OMe,1-methyloxy-2-methylpropyl), (B344, F, F, Me, OMe, 1-methyloxypentyl),(B345, F, F, Me, OMe, 1-methyloxy-3-methylbutyl), (B346, F, F, Me, OMe,1-methyloxy-2,2-dimethylpropyl), (B350, F, F, Me, OMe,1-methyloxyheptyl), (B351, F, F, Me, OMe, 1-methyloxyoctyl), (B352, F,F, Me, OMe, 3-methyloxyoctyl), (B353, F, F, Me, OMe, 1-methyloxynonyl),(B356, F, F, Me, OMe, 1-methyloxydodecyl), (B357, F, F, Me, OMe,1-methyloxy-1-cyclohexylmethyl), (B358, F, F, Me, OMe,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B359, F, F, Me, OMe,1-ethyloxyethyl), (B360, F, F, Me, OMe, 1-(4-ethyloxybutyloxy)propyl),(B361, F, F, Me, OMe, 1-(4-ethyloxypropyl), (B362, F, F, Me, OMe,1-ethyloxy-3-n-hexyloxypropyl), (B363, F, F, Me, OMe, 1-ethyloxybutyl),(B364, F, F, Me, OMe, 1-ethyloxy-3-n-pentylbutyl), (B365, F, F, Me, OMe,1-ethyloxy-2-methylpropyl), (B366, F, F, Me, OMe, 1-ethyloxypentyl),(B367, F, F, Me, OMe, 1-ethyloxy-3-methylbutyl), (3368, F, F, Me, OMe,1-ethyloxy-2,2-dimethylpropyl), (B369, F, F, Me, OMe, 1-ethyloxyhexyl),(3370, F, F, Me, OMe, 1-ethyloxy-3,3-dimethylbutyl), (B371, F, F, Me,OMe, 1-ethyloxyheptyl), (B372, F, F, Me, OMe, 1-ethyloxyoctyl), (B373,F, F, Me, OMe, 1-ethyloxynonyl), (B374, F, F, Me, OMe, 1-ethyloxydecyl),(B375, F, F, Me, OMe, 1-ethyloxyundecyl), (B376, F, F, Me, OMe,1-ethyloxydodecyl), (B377, F, F, Me, OMe,1-ethyloxy-1-cyclohexylmethyl), (B378, F, F, Me, OMe,1-n-propyloxyethyl), (B379, F, F, Me, OMe, 1-n-propyloxypropyl), (B381,F, F, Me, OMe, 1-n-propyloxy-3-n-hexyloxypropyl), (B382, F, F, Me, OMe,1-n-propyloxybutyl), (B383, F, F, Me, OMe,1-n-propyloxy-4-n-pentyloxybutyl), (B384, F, F, Me, OMe,1,4-di(n-propyloxy)butyl), (3385, F, F, Me, OMe,1-n-propyloxy-2-methylpropyl), (B386, F, F, Me, OMe,1-n-propyloxypentyl), (B387, F, F, Me, OMe,1-n-propyloxy-3-methylbutyl), (B388, F, F, Me, OMe,1-n-propyloxy-2,2-dimethylpropyl), (B389, F, F, Me, OMe,1-n-propyloxyhexyl), (B390, F, F, Me, OMe,1-n-propyloxy-3,3-dimethylbutyl), (B391, F, F, Me, OMe,1-n-propyloxyheptyl), (B392, F, F, Me, OMe, 1-n-propyloxyoctyl), (B393,F, F, Me, OMe, 1-n-propyloxynonyl), (B394, F, F, Me, OMe,1-n-propyloxydecyl), (B395, F, F, Me, OMe, 1-n-propyloxyundecyl), (B396,F, F, Me, OMe, 1-n-propyloxydodecyl), (B398, F, F, Me, OMe,1-isopropyloxyethyl), (B399, F, F, Me, OMe, 1-isopropyloxypropyl),(B400, F, F, Me, OMe, 3-isopropyloxypropyl), (B401, F, F, Me, OMe,1-isopropyloxy-3-n-hexyloxypropyl), (B402, F, F, Me, OMe,1-isopropyloxybutyl), (B403, F, F, Me, OMe,1-isopropyloxy-4-n-pentyloxybutyl), (1B404, F, F, Me, OMe,1-isopropyloxy-2-methylpropyl), (B405, F, F, Me, OMe,1-isopropyloxypentyl), (B406, F, F, Me, OMe,1-isopropyloxy-3-methylbutyl), (B407, F, F, Me, OMe,1-isopropyloxy-2,2-dimethylpropyl), (B408, F, F, Me, OMe,1-isopropyloxyhexyl), (B409, F, F, Me, OMe,1-isopropyloxy-3,3-dimethylbutyl), (B410, F, F, Me, OMe,1-isopropyloxyheptyl), (B411, F, F, Me, OMe, 1-isopropyloxyoctyl),(B412, F, F, Me, OMe, 1-isopropyloxynonyl), (B413, F, F, Me, OMe,1-isopropyloxydecyl), (B414, F, F, Me, OMe, 1-isopropyloxyundecyl),(B415, F, F, Me, OMe, 1-isopropyloxydodecyl), (B416, F, F, Me, OMe,1-isopropyloxy-1-cyclohexylmethyl), (B417, F, F, Me, OMe,1-n-butyloxyethyl), (B420, F, F, Me, OMe, 1-n-butyloxybutyl), (B421, F,F, Me, OMe, 1,4-di(n-butyloxy)butyl), (B422, F, F, Me, OMe,1-n-butyloxy-2-methylpropyl), (B423, F, F, Me, OMe, 1-n-butyloxypentyl),(B424, F, F, Me, OMe, 1-n-butyloxy-3-methylbutyl), (B426, F, F, Me, OMe,1-n-butyloxyhexyl), (B427, F, F, Me, OMe,1-n-butyloxy-3,3-dimethylbutyl), (B428, F, F, Me, OMe,1-n-butyloxyheptyl), (B429, F, F, Me, OMe, 1-n-butyloxyoctyl), (B430, F,F, Me, OMe, 1-n-butyloxynonyl), (B431, F, F, Me, OMe,1-n-butyloxydecyl), (B432, F, F, Me, OMe, 1-n-butyloxyundecyl), (B433,F, F, Me, OMe, 1-n-butyloxydodecyl), (B434, F, F, Me, OMe,1-n-butyloxy-1-cyclohexylmethyl), (B435, F, F, Me, OMe,1-isobutyloxyethyl), (B436, F, F, Me, OMe, 1-isobutyloxypropyl), (B437,F, F, Me, OMe, 1-isobutyloxybutyl), (B438, F, F, Me, OMe,1-isobutyloxy-2-methylpropyl), (B439, F, F, Me, OMe,1-isobutyloxypentyl), (B440, F, F, Me, OMe,1-isobutyloxy-3-methylbutyl), (B441, F, F, Me, OMe,1-isobutyloxy-2,2-dimethylpropyl), (B442, F, F, Me, OMe,1-isobutyloxyhexyl), (B443, F, F, Me, OMe,1-isobutyloxy-3,3-dimethylbutyl), (B444, F, F, Me, OMe,1-isobutyloxyheptyl), (B445, F, F, Me, OMe, 1-isobutyloxyoctyl), (B446,F, F, Me, OMe, 1-isobutyloxyynonyl), (B447, F, F, Me, OMe,1-isobutyloxydecyl), (B448, F, F, Me, OMe, 1-isobutyloxyundecyl), (B449,F, F, Me, OMe, 1-isobutyloxydodecyl), (B450, F, F, Me, OMe,1-isobutyloxy-1-cyclohexylmethyl), (B451, F, F, Me, OMe,1-t-butyloxyethyl), (B452, F, F, Me, OMe, 1-t-butyloxypropyl), (B453, F,F, Me, OMe, 1-t-butyloxybutyl), (B454, F, F, Me, OMe,1-t-butyloxy-2-methylpropyl), (B455, F, F, Me, OMe, 1-t-butyloxypentyl),(B456, F, F, Me, OMe, 1-t-butyloxy-3-methylbutyl), (B457, F, F, Me, OMe,1-t-butyloxy-2,2-dimethylpropyl), (B458, F, F, Me, OMe,1-t-butyloxyhexyl), (B459, F, F, Me, OMe,1-t-butyloxy-3,3-dimethylbutyl), (B460, F, F, Me, OMe,1-t-butyloxyheptyl), (B461, F, F, Me, OMe, 1-t-butyloxyoctyl), (B462, F,F, Me, OMe, 1-t-butyloxynonyl), (B463, F, F, Me, OMe,1-t-butyloxydecyl), (B464, F, F, Me, OMe, 1-t-butyloxyundecyl), (B465,F, F, Me, OMe, 1-t-butyloxydodecyl), (B466, F, F, Me, OMe,1-t-butyloxy-1-cyclohexylmethyl), (B467, F, F, Me, OMe,1-n-pentyloxyethyl), (B468, F, F, Me, OMe, 1-n-pentyloxypropyl), (B469,F, F, Me, OMe, 3-n-pentyloxypropyl), (B470, F, F, Me, OMe,1-n-pentyloxy-3-methylthiopropyl), (B471, F, F, Me, OMe,1-n-pentyloxybutyl), (B472, F, F, Me, OMe,1-n-pentyloxy-2-methylpropyl), (B473, F, F, Me, OMe,1-n-pentyloxypentyl), (B474, F, F, Me, OMe,1-n-pentyloxy-3-methylbutyl), (B475, F, F, Me, OMe,1-n-pentyloxy-2,2-dimethylpropyl), (B476, F, F, Me, OMe,1-n-pentyloxyhexyl), (B477, F, F, Me, OMe,1-n-pentyloxy-3,3-dimethylbutyl), (B478, F, F, Me, OMe,1-n-pentyloxyheptyl), (B479, F, F, Me, OMe, 1-n-pentyloxyoctyl), (B480,F, F, Me, OMe, 1-n-pentyloxynonyl), (B481, F, F, Me, OMe,1-n-pentyloxydecyl), (B482, F, F, Me, OMe, 1-n-pentyloxyundecyl), (B483,F, F, Me, OMe, 1-n-pentyloxydodecyl), (B484, F, F, Me, OMe,1-n-pentyloxyl-cyclohexylmethyl), (B485, F, F, Me, OMe,1-isopentyloxypropyl), (B486, F, F, Me, OMe, 1-neopentyloxyethyl),(B487, F, F, Me, OMe, 1-neopentyloxypropyl), (B3489, F, F, Me, OMe,1-neopentyloxybutyl), (B7490, F, F, Me, OMe,1-neopentyloxy-2-methylpropyl), (B491, F, F, Me, OMe,1-neopentyloxypentyl), (B492, F, F, Me, OMe,1-neopentyloxy-3-methylbutyl), (B493, F, F, Me, OMe,1-neopentyloxy-2,2-dimethylpropyl), (B494, F, F, Me, OMe,1-neopentyloxyhexyl), (B495, F, F, Me, OMe,1-neopentyloxy-3,3-dimethylbutyl), (B496, F, F, Me, OMe,1-neopentyloxyheptyl), (B497, F, F, Me, OMe, 1-neopentyloxyoctyl),(B498, F, F, Me, OMe, 1-neopentyloxynonyl), (B499, F, F, Me, OMe,1-neopentyloxydecyl), (B500, F, F, Me, OMe, 1-neopentyloxyundecyl),(B501, F, F, Me, OMe, 1-neopentyloxydodecyl), (B502, F, F, Me, OMe,1-neopentyloxy-1-cyclohexylmethyl), (B503, F, F, Me, OMe,1-n-hexyloxyethyl), (B504, F, F, Me, OMe, 1-n-hexyloxypropyl), (B506, F,F, Me, OMe, 1-n-hexyloxybutyl), (B507, F, F, Me, OMe,1-n-hexyloxy-2-methylpropyl), (B508, F, F, Me, OMe, 1-n-hexyloxypentyl),(B509, F, F, Me, OMe, 1-n-hexyloxy-3-methylbutyl), (B510, F, F, Me, OMe,1-n-hexyloxy-2,2-dimethylpropyl), (B511, F, F, Me, OMe,1-n-hexyloxyhexyl), (B512, F, F, Me, OMe,1-n-hexyloxy-3,3-dimethylbutyl), (B513, F, F, Me, OMe,1-n-hexyloxyheptyl), (B514, F, F, Me, OMe, 1-n-hexyloxyoctyl), (B515, F,F, Me, OMe, 1-n-hexyloxynonyl), (B516, F, F, Me, OMe,1-n-hexyloxydecyl), (B517, F, F, Me, OMe, 1-n-hexyloxyundecyl), (B518,F, F, Me, OMe, 1-n-hexyloxydodecyl), (B520, F, F, Me, OMe,3-isohexyloxydodecyl), (B522, F, F, Me, OMe,3-(2-cycdopentylethyloxy)propyl), (B523, F, F, Me, OMe,1-n-octyloxydodecyl), (B524, F, F, OMe, F, 1-methyloxyethyl), (B525, F,F, OMe, F, 1-methyloxypropyl), (B526, F, F, OMe, F,1-methyloxy-3-n-hexyloxypropyl), (B527, F, F, OMe, F, 1-methyloxybutyl),(B528, F, F, OMe, F, 1-methyloxy-4-n-pentyloxybutyl), (B529, F, F, OMe,F, 1-methyloxy-2-methylpropyl), (B530, F, F, OMe, F, 1-methyloxypentyl),(B531, F, F, OMe, F, 1-methyloxy-3-methylbutyl), (B532, F, F, OMe, F,1-methyloxy-2,2-dimethylpropyl), (B534, F, F, OMe, F, 4-methyloxyhexyl),(B535, F, F, OMe, F, 1-methyloxy-4-methylpentyl), (B536, F, F, OMe, F,1-methyloxy-3,3-dimethylbutyl), (B537, F, F, OMe, F,3-methyloxy-2,4-dimethyl-3-pentyl), (B538, F, F, OMe, F,1-methyloxyheptyl), (B539, F, F, OMe, F, 4-methyloxy-4-heptyl), (B540,F, F, OMe, F, 1-methyloxyoctyl), (B541, F, F, OMe, F, 3-methyloxyoctyl),(B542, F, F, OMe, F, 1-methyloxynonyl), (B543, F, F, OMe, F,1-methyloxydecyl), (B544, F, F, OMe, F, 1-methyloxyundecyl), (B545, F,F, OMe, F, 1-methyloxydodecyl), (B546, F, F, OMe, F,1-methyloxy-1-cyclohexylmethyl), (B547, F, F, OMe, F,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B548, F, F, OMe, F,1-ethyloxyethyl), (B549, F, F, OMe, F, 1-ethyloxypropyl), (B550, F, F,OMe, F, 1-ethyloxy-3-n-hexyloxypropyl), (13551, F, F, OMe, F,1-(4-ethyloxybutyloxy)propyl), (B552, F, F, OMe, F, 1-ethyloxybutyl),(B553, F, F, OMe, F, 1-ethyloxy-4-n-pentyloxybutyl), (B554, F, F, OMe,F, 1-ethyloxy-2-methylpropyl), (B555, F, F, OMe, F, 1-ethyloxypentyl),(B556, F, F, OMe, F, 1-ethyloxy-3-methylbutyl), (B557, F, F, OMe, F,1-ethyloxy-2,2-dimethylpropyl), (B558, F, F, OMe, F, 1-ethyloxyhexyl),(B559, F, F, OMe, F, 1-ethyloxy-3,3-dimethylbutyl), (B560, F, F, OMe, F,1-ethyloxyheptyl), (B561, F, F, OMe, F, 1-ethyloxyoctyl), (B562, F, F,OMe, F, 1-ethyloxynonyl), (B563, F, F, OMe, F, 1-ethyloxydecyl), (B564,F, F, OMe, F, 1-ethyloxyundecyl), (B565, F, F, OMe, F,1-ethyloxydodecyl), (B566, F, F, OMe, F, 1-ethyloxy-1-cyclohexylmethyl),(B567, F, F, OMe, F, 1-n-propyloxyethyl), (B568, F, F, OMe, F,1-n-propyloxypropyl), (B569, F, F, OMe, F, 3-n-propyloxypropyl), (B570,F, F, OMe, F, 1-n-propyloxy-3-n-hexyloxypropyl), (B571, F, F, OMe, F,1-n-propyloxybutyl), (B572, F, F, OMe, F,1-n-propyloxy-4-n-pentyloxybutyl), (B573, F, F, OMe, F,1,4-di(n-propyloxy)butyl), (B574, F, F, OMe, F,1-n-propyloxy-2-methylpropyl), (B575, F, F, OMe, F,1-n-propyloxypentyl), (B576, F, F, OMe, F, 1-n-propyloxy-3-methylbutyl),(B577, F, F, OMe, F, 1-n-propyloxy-2,2-dimethylpropyl), (B578, F, F,OMe, F, 1-n-propyloxyhexyl), (B579, F, F, OMe, F,1-n-propyloxy-3,3-dimethylbutyl), (B580, F, F, OMe, F,1-n-propyloxyheptyl), (B581, F, F, OMe, F, 1-n-propyloxyoctyl), (B582,F, F, OMe, F, 1-n-propyloxynonyl), (B583, F, F, OMe, F,1-n-propyloxydecyl), (B584, F, F, OMe, F, 1-n-propyloxyundecyl), (B585,F, F, OMe, F, 1-n-propyloxydodecyl), (B586, F, F, OMe, F,1-n-propyloxy-1-cyclohexylmethyl), (B587, F, F, OMe, F,1-isopropyloxyethyl), (B588, F, F, OMe, F, 1-isopropyloxypropyl), (B589,F, F, OMe, F, 3-isopropyloxypropyl), (B590, F, F, OMe, F,1-isopropyloxy-3-n-hexyloxypropyl), (B591, F, F, OMe, F,1-isopropyloxybutyl), (B592, F, F, OMe, F,1-isopropyloxy-4-n-pentyloxybutyl), (B593, F, F, OMe, F,1-isopropyloxy-2-methylpropyl), (B594, F, F, OMe, F,1-isopropyloxypentyl), (B595, F, F, OMe, F,1-isopropyloxy-3-methylbutyl), (B596, F, F, OMe, F,1-isopropyloxy-2,2-dimethylpropyl), (B597, F, F, OMe, F,1-isopropyloxyhexyl), (B598, F, F, OMe, F,1-isopropyloxy-3,3-dimethylbutyl), (B599, F, F, OMe, F,1-isopropyloxyheptyl), (B600, F, F, OMe, F, 1-isopropyloxyoctyl), (B601,F, F, OMe, F, 1-isopropyloxynonyl), (B602, F, F, OMe, F,1-isopropyloxydecyl), (B603, F, F, OMe, F, 1-isopropyloxyundecyl),(B604, F, F, OMe, F, 1-isopropyloxydodecyl), (B605, F, F, OMe, F,1-isopropyloxy-1-cyclohexylmethyl), (B606, F, F, OMe, F,1-n-butyloxyethyl), (B607, F, F, OMe, F, 1-n-butyloxypropyl), (B608, F,F, OMe, F, 3-n-butyloxypropyl), (B609, F, F, OMe, F, 1-n-butyloxybutyl),(B610, F, F, OMe, F, 1,4-di(n-butyloxy)butyl), (B611, F, F, OMe, F,1-n-butyloxy-2-methylpropyl), (B612, F, F, OMe, F, 1-n-butyloxypentyl),(B613, F, F, OMe, F, 1-n-butyloxy-3-methylbutyl), (B614, F, F, OMe, F,1-n-butyloxy-2,2-dimethylpropyl), (B615, F, F, OMe, F,1-n-butyloxyhexyl), (B616, F, F, OMe, F,1-n-butyloxy-3,3-dimethylbutyl), (B617, F, F, OMe, F,1-n-butyloxyheptyl), (B618, F, F, OMe, F, 1-n-butyloxyoctyl), (B619, F,F, OMe, F, 1-n-butyloxynonyl), (B620, F, F, OMe, F, 1-n-butyloxydecyl),(B621, F, F, OMe, F, 1-n-butyloxyundecyl), (B622, F, F, OMe, F,1-n-butyloxydodecyl), (B623, F, F, OMe, F,1-n-butyloxy-1-cyclohexylmethyl), (B624, F, F, OMe, F,1-isobutyloxyethyl), (B625, F, F, OMe, F, 1-isobutyloxypropyl), (B626,F, F, OMe, F, 1-isobutyloxybutyl), (B627, F, F, OMe, F,1-isobutyloxy-2-methylpropyl), (B628, F, F, OMe, F,1-isobutyloxypentyl), (B629, F, F, OMe, F, 1-isobutyloxy-3-methylbutyl),(B630, F, F, OMe, F, 1-isobutyloxy-2,2-dimethylpropyl), (B631, F, F,OMe, F, 1-isobutyloxyhexyl), (B632, F, F, OMe, F,1-isobutyloxy-3,3-dimethylbutyl), (B633, F, F, OMe, F,1-isobutyloxyheptyl), (B634, F, F, OMe, F, 1-isobutyloxyoctyl), (B635,F, F, OMe, F, 1-isobutyloxyynonyl), (B636, F, F, OMe, F,1-isobutyloxydecyl), (B637, F, F, OMe, F, 1-isobutyloxyundecyl), (B638,F, F, OMe, F, 1-isobutyloxydodecyl), (B639, F, F, OMe, F,1-isobutyloxy-1-cyclohexylmethyl), (B640, F, F, OMe, F,1-t-butyloxyethyl), (B641, F, F, OMe, F, 1-t-butyloxypropyl), (B642, F,F, OMe, F, 1-t-butyloxybutyl), (13643, F, F, OMe, F,1-t-butyloxy-2-methylpropyl), (B644, F, F, OMe, F, 1-t-butyloxypentyl),(B645, F, F, OMe, F, 1-t-butyloxy-3-methylbutyl), (B646, F, F, OMe, F,1-t-butyloxy-2,2-dimethylpropyl), (B647, F; F, OMe, F,1-t-butyloxyhexyl), (B648, F, F, OMe, F,1-t-butyloxy-3,3-dimethylbutyl), (1B649, F, F, OMe, F,1-t-butyloxyheptyl), (B650, F, F, OMe, F, 1-t-butyloxyoctyl), (B651, F;F, OMe, F, 1-t-butyloxynonyl), (B652, F, F, OMe, F, 1-t-butyloxydecyl),(B653, F, F, OMe, F, 1-t-butyloxyundecyl), (B654, F, F, OMe, F,1-t-butyloxydodecyl), (B655, F, F, OMe, F,1-t-butyloxy-1-cyclohexylmethyl), (B656, F, F, OMe, F,1-n-pentyloxyethyl), (B657, F, F, OMe, F, 1-n-pentyloxypropyl), (B658,F, F, OMe, F, 3-n-pentyloxypropyl), (B659, F, F, OMe, F,1-n-pentyloxy-3-methylthiopropyl), (13660, F, F, OMe, F,1-n-pentyloxybutyl), (B661, F, F, OMe, F, 1-n-pentyloxy-2-methylpropyl),(B662, F, F, OMe, F, 1-n-pentyloxypentyl), (B663, F, F, OMe, F,1-n-pentyloxy-3-methylbutyl), (B664, F, F, OMe, F,1-n-pentyloxy-2,2-dimethylpropyl), (B665, F, F, OMe, F,1-n-pentyloxyhexyl), (13666, F, F, OMe, F,1-n-pentyloxy-3,3-dimethylbutyl), (B667, F, F, OMe, F,1-n-pentyloxyheptyl), (1668, F, F, OMe, F, 1-n-pentyloxyoctyl), (B669,F, F, OMe, F, 1-n-pentyloxynonyl), (B670, F, F, OMe, F,1-n-pentyloxydecyl), (B671, F, F, OMe, F, 1-n-pentyloxyundecyl), (B672,F, F, OMe, F, 1-n-pentyloxydodecyl), (B673, F, F, OMe, F,1-n-pentyloxy-1-cyclohexylmethyl), (B674, F, F, OMe, F,1-isopentyloxyproyl), (B675, F, F, OMe, F, 1-neopentyloxyethyl), (B676,F, F, OMe, F, 1-neopentyloxypropyl), (B677, F, F, OMe, F,1-neopentyloxybutyl), (B678, F, F, OMe, F,1-neopentyloxy-2-methylpropyl), (B679, F, F, OMe, F,1-neopentyloxypentyl), (B680, F, F, OMe, F,1-neopentyloxy-3-methylbutyl), (B681, F, F, OMe, F,1-neopentyloxy-2,2-dimethylpropyl), (B682, F, F, OMe, F,1-neopentyloxyhexyl), (B683, F, F, OMe, F,1-neopentyloxy-3,3-dimethylbutyl), (B684, F, F, OMe, F,1-neopentyloxyheptyl), (B685, F, F, OMe, F, 1-neopentyloxyoctyl), (B686,F, F, OMe, F, 1-neopentyloxynonyl), (B687, F, F, OMe, F,1-neopentyloxydecyl), (B688, F, F, OMe, F, 1-neopentyloxyundecyl),(B689, F, F, OMe, F, 1-neopentyloxydodecyl), (B690, F, F, OMe, F,1-neopentyloxy-1-cyclohexylmethyl), (B691, F, F, OMe, F,1-n-hexyloxyethyl), (B692, F, F, OMe, F, 1-n-hexyloxypropyl), (B693, F,F, OMe, F, 3-n-hexyloxypropyl), (B694, F, F, OMe, F, 1-n-hexyloxybutyl),(B695, F, F, OMe, F, 1-n-hexyloxy-2-methylpropyl), (B696, F, F, OMe, F,1-n-hexyloxypentyl), (B697, F, F, OMe, F, 1-n-hexyloxy-3-methylbutyl),(B698, F, F, OMe, F, 1-n-hexyloxy-2,2-dimethylpropyl), (B699, F, F, OMe,F, 1-n-hexyloxyhexyl), (B700, F, F, OMe, F,1-n-hexyloxy-3,3-dimethylbutyl), (B701, F, F, OMe, F,1-n-hexyloxyheptyl), (B702, F, F, OMe, F, 1-n-hexyloxyoctyl), (B703, F,F, OMe, F, 1-n-hexyloxynonyl), (B704, F, F, OMe, F, 1-n-hexyloxydecyl),(B705, F, F, OMe, F, 1-n-hexyloxyundecyl), (B706, F, F, OMe, F,1-n-hexyloxydodecyl), (3707, F, F, OMe, F,1-n-hexyloxy-1-cyclohexylmethyl), (B708, F, F, OMe, F,3-isohexyloxyproyl), (B709, F, F, OMe, F,3-(3,3-dimethylbutyloxy)propyl), (B710, F, F, OMe, F,3-(2-cyclopentylethyloxy)propyl), (B711, F, F, OMe, F,1-n-octyloxydodecyl), (B712, F, F, OMe, OMe, 1-methyloxyethyl), (B713,F, F, OMe, OMe, 1-methyloxypropyl), (B714, F, F, OMe, OMe,1-methyloxy-3-n-hexyloxypropyl), (B715, F, F, OMe, OMe,1-methyloxybutyl), (B716, F, F, OMe, OMe,1-methyloxy-4-n-pentyloxybutyl), (B717, F, F, OMe, OMe,1-methyloxy-2-methylpropyl), (B718, F, F, OMe, OMe, 1-methyloxypentyl),(B719, F, F, OMe, OMe, 1-methyloxy-3-methylbutyl), (B720, F, F, OMe,OMe, 1-methyloxy-2,2-dimethylpropyl), (B721, F, F, OMe, OMe,1-methyloxyhexyl), (B722, F, F, OMe, OMe, 4-methyloxyhexyl), (B723, F,F; OMe, OMe, 1-methyloxy-4-methylpentyl), (B724, F, F, OMe, OMe,1-methyloxy-3,3-dimethylbutyl), (B725, F, F, OMe, OMe,3-methyloxy-2,4-dimethyl-3-pentyl), (B726, F, F, OMe, OMe,1-methyloxyheptyl), (B727, F, F, OMe, OMe, 4-methyloxy-4-heptyl), (B728,F, F, OMe, OMe, 1-methyloxyoctyl), (B729, F, F, OMe, OMe,3-methyloxyoctyl), (B730, F, F, OMe, OMe, 1-methyloxynonyl), (B731, F,F, OMe, OMe, 1-methyloxydecyl), (B732, F, F, OMe, OMe,1-methyloxyundecyl), (B733, F, F, OMe, OMe, 1-methyloxydodecyl), (B734,F, F, OMe, OMe, 1-methyloxy-1-cyclohexylmethyl), (B735, F, F, OMe, OMe,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B736, F, F, OMe, OMe,1-ethyloxyethyl), (B737, F, F, OMe, OMe, 1-ethyloxypropyl), (B738, F, F,OMe, OMe, 1-(4-ethyloxybutyloxy)propyl), (B739, F, F, OMe, OMe,1-ethyloxybutyl), (B740, F, F, OMe, OMe, 1-ethyloxy-2-methylpropyl),(B741, F, F, OMe, OMe, 1-ethyloxypentyl), (B742, F, F, OMe, OMe,1-ethyloxy-3-methylbutyl), (B743, F, F, OMe, OMe,1-ethyloxy-2,2-dimethylpropyl), (B744, F, F, OMe, OMe, 1-ethyloxyhexyl),(B745, F, F, OMe, OMe, 1-ethyloxy-3,3-dimethylbutyl), (B746, F, F, OMe,OMe, 1-ethyloxyheptyl), (B747, F, F, OMe, OMe, 1-ethyloxyoctyl), (B3748,F, F, OMe, OMe, 1-ethyloxynonyl), (B749, F, F, OMe, OMe,1-ethyloxydecyl), (B750, F, F, OMe, OMe, 1-ethyloxyundecyl), (B751, F,F, OMe, OMe, 1-ethyloxydodecyl), (B752, F, F, OMe, OMe,1-ethyloxy-1-cyclohexylmethyl), (B753, F, F, OMe, OMe,1-n-propyloxyethyl), (B754, F, F, OMe, OMe, 1-n-propyloxypropyl), (B755,F, F, OMe, OMe, 3-n-propyloxypropyl), (B756, F, F, OMe, OMe,1-n-propyloxybutyl), (B757, F, F, OMe, OMe, 1,4-di(n-propyloxy)butyl),(B758, F, F, OMe, OMe, 1-n-propyloxy-2-methylpropyl), (B759, F, F, OMe,OMe, 1-n-propyloxypentyl), (B760, F, F, OMe, OMe,1-n-propyloxy-3-methylbutyl), (B761, F, F, OMe, OMe,1-n-propyloxy-2,2-dimethylpropyl), (B762, F, F, OMe, OMe,1-n-propyloxyhexyl), (B763, F, F, OMe, OMe,1-n-propyloxy-3,3-dimethylbutyl), (B764, F, F, OMe, OMe,1-n-propyloxyheptyl), (B765, F, F, OMe, OMe, 1-n-propyloxyoctyl), (B766,F, F, OMe, OMe, 1-n-propyloxynonyl), (B767, F, F, OMe, OMe,1-n-propyloxydecyl), (B768, F, F, OMe, OMe, 1-n-propyloxyundecyl),(B769, F, F, OMe, OMe, 1-n-propyloxydodecyl), (B770, F, F, OMe, OMe,1-n-propyloxy-1-cyclohexylmethyl), (B771, F, F, OMe, OMe,1-isopropyloxyethyl), (B772, F, F, OMe, OMe, 1-isopropyloxypropyl),(B773, F, F, OMe, OMe, 3-isopropyloxypropyl), (B774, F, F, OMe, OMe,1-isopropyloxybutyl), (B775, F, F, OMe, OMe,1-isopropyloxy-2-methylpropyl), (13776, F, F, OMe, OMe,1-isopropyloxypentyl), (B777, F, F, OMe, OMe,1-isopropyloxy-3-methylbutyl), (B778, F, F, OMe, OMe,1-isopropyloxy-2,2-dimethylpropyl), (B779, F, F, OMe, OMe,1-isopropyloxyhexyl), (B780, F, F, OMe, OMe,1-isopropyloxy-3,3-dimethylbutyl), (B781, F, F, OMe, OMe,1-isopropyloxyheptyl), (B782, F, F, OMe, OMe, 1-isopropyloxyoctyl),(B783, F, F, OMe, OMe, 1-isopropyloxynonyl), (B784, F, F, OMe, OMe,1-isopropyloxydecyl), (1B785, F, F, OMe, OMe, 1-isopropyloxyundecyl),(B786, F, F, OMe, OMe, 1-isopropyloxydodecyl), (B787, F, F, OMe, OMe,1-isopropyloxy-1-cyclohexylmethyl), (B788, F, F, OMe, OMe,1-n-butyloxyethyl), (B789, F, F, OMe, OMe, 1-n-butyloxypropyl), (B791,F, F, OMe, OMe, 1-n-butyloxybutyl), (B792, F, F, OMe, OMe,1,4-di(n-butyloxy)butyl), (B793, F, F, OMe, OMe,1-n-butyloxy-2-methylpropyl), (B794, F, F, OMe, OMe,1-n-butyloxypentyl), (B795, F, F, OMe, OMe, 1-n-butyloxy-3-methylbutyl),(B796, F, F, OMe, OMe, 1-n-butyloxy-2,2-dimethylpropyl), (B797, F, F,OMe, OMe, 1-n-butyloxyhexyl), (3798, F, F, OMe, OMe,1-n-butyloxy-3,3-dimethylbutyl), (B799, F, F, OMe, OMe,1-n-butyloxyheptyl), (B800, F, F, OMe, OMe, 1-n-butyloxyoctyl), (B801,F, F, OMe, OMe, 1-n-butyloxynonyl), (B802, F, F, OMe, OMe,1-n-butyloxydecyl), (B803, F, F, OMe, OMe, 1-n-butyloxyundecyl), (B804,F, F, OMe, OMe, 1-n-butyloxydodecyl), (B805, F, F, OMe, OMe,1-n-butyloxy-1-cyclohexylmethyl), (B806, F, F, OMe, OMe,1-isobutyloxyethyl), (B807, F, F, OMe, OMe, 1-isobutyloxypropyl), (B808,F, F, OMe, OMe, 1-isobutyloxybutyl), (B809, F, F, OMe, OMe,1-isobutyloxy-2-methylpropyl), (B810, F, F, OMe, OMe,1-isobutyloxypentyl), (B811, F, F, OMe, OMe,1-isobutyloxy-3-methylbutyl), (B812, F, F, OMe, OMe,1-isobutyloxy-2,2-dimethylpropyl), (B813, F, F, OMe, OMe,1-isobutyloxyhexyl), (B814, F, F, OMe, OMe,1-isobutyloxy-3,3-dimethylbutyl), (B815, F, F, OMe, OMe,1-isobutyloxyheptyl), (B816, F, F, OMe, OMe, 1-isobutyloxyoctyl), (B817,F, F, OMe, OMe, 1-isobutyloxyynonyl), (B818, F, F, OMe, OMe,1-isobutyloxydecyl), (B819, F, F, OMe, OMe, 1-isobutyloxyundecyl),(B820, F, F, OMe, OMe, 1-isobutyloxydodecyl), (B821, F, F, OMe, OMe,1-isobutyloxy-1-cyclohexylmethyl), (B822, F, F, OMe, OMe,1-t-butyloxyethyl), (B823, F, F, OMe, OMe, 1-t-butyloxypropyl), (B824,F, F, OMe, OMe, 1-t-butyloxybutyl), (B825, F, F, OMe, OMe,1-t-butyloxy-2-methylpropyl), (B826, F, F, OMe, OMe,1-t-butyloxypentyl), (B827, F, F, OMe, OMe, 1-t-butyloxy-3-methylbutyl),(B828, F, F, OMe, OMe, 1-t-butyloxy-2,2-dimethylpropyl), (B829, F, F,OMe, OMe, 1-t-butyloxyhexyl), (B830, F, F, OMe, OMe,1-t-butyloxy-3,3-dimethylbutyl), (B831, F, F, OMe, OMe,1-t-butyloxyheptyl), (B832, F, F, OMe, OMe, 1-t-butyloxyoctyl), (B833,F, F, OMe, OMe, 1-t-butyloxynonyl), (B834, F, F, OMe, OMe,1-t-butyloxydecyl), (B835, F, F, OMe, OMe, 1-t-butyloxyundecyl), (B836,F, F, OMe, OMe, 1-t-butyloxydodecyl), (B837, F, F, OMe, OMe,1-t-butyloxy-1-cyclohexylmethyl), (B838, F, F, OMe, OMe,1-n-pentyloxyethyl), (B839, F, F, OMe, OMe, 1-n-pentyloxypropyl), (B840,F, F, OMe, OMe, 3-n-pentyloxypropyl), (B841, F, F, OMe, OMe,1-n-pentyloxy-3-methylthiopropyl), (B842, F, F, OMe, OMe,1-n-pentyloxybutyl), (B843, F, F, OMe, OMe,1-n-pentyloxy-2-methylpropyl), (B844, F, F, OMe, OMe,1-n-pentyloxypentyl), (B845, F, F, OMe, OMe,1-n-pentyloxy-3-methylbutyl), (B846, F, F, OMe, OMe,1-n-pentyloxy-2,2-dimethylpropyl), (B847, F, F, OMe, OMe,1-n-pentyloxyhexyl), (B848, F, F, OMe, OMe,1-n-pentyloxy-3,3-dimethylbutyl), (B849, F, F, OMe, OMe,1-n-pentyloxyheptyl), (B850, F, F, OMe, OMe, 1-n-pentyloxyoctyl), (B851,F, F, OMe, OMe, 1-n-pentyloxynonyl), (B852, F, F, OMe, OMe,1-n-pentyloxydecyl), (B853, F, F, OMe, OMe, 1-n-pentyloxyundecyl),(B854, F, F, OMe, OMe, 1-n-pentyloxydodecyl), (B855, F, F, OMe, OMe,1-n-pentyloxy-1-cyclohexylmethyl), (B856, F, F, OMe, OMe,1-isopentyloxypropyl), (3857, F, F, OMe, OMe, 1-neopentyloxyethyl),(B858, F, F, OMe, OMe, 1-neopentyloxypropyl), (B859, F, F, OMe, OMe,3-neopentyloxyethyl), (B860, F, F, OMe, OMe, 1-neopentyloxybutyl),(B861, F, F, OMe, OMe, 1-neopentyloxy-2-methylpropyl), (B862, F, F, OMe,OMe, 1-neopentyloxypentyl), (B863, F, F, OMe, OMe,1-neopentyloxy-3-methylbutyl), (B864, F, F, OMe, OMe,1-neopentyloxy-2,2-dimethylpropyl), (B865, F, F, OMe, OMe,1-neopentyloxyhexyl), (B866, F, F, OMe, OMe,1-neopentyloxy-3,3-dimethylbutyl), (B867, F, F, OMe, OMe,1-neopentyloxyheptyl), (B868, F, F, OMe, OMe, 1-neopentyloxyoctyl),(B869, F, F, OMe, OMe, 1-neopentyloxynonyl), (B870, F, F, OMe, OMe,1-neopentyloxydecyl), (13871, F, F, OMe, OMe, 1-neopentyloxyundecyl),(B872, F, F, OMe, OMe, 1-neopentyloxydodecyl), (B873, F, F, OMe, OMe,1-neopentyloxy-1-cyclohexylmethyl), (B874, F, F, OMe, OMe,1-n-hexyloxyethyl), (B875, F, F, OMe, OMe, 1-n-hexyloxypropyl), (B876,F, F, OMe, OMe, 3-n-hexyloxypropyl), (B877, F, F, OMe, OMe,1-n-hexyloxybutyl), (B878, F, F, OMe, OMe, 1-n-hexyloxy-2-methylpropyl),(B879, F, F, OMe, OMe, 1-n-hexyloxypentyl), (B880, F, F, OMe, OMe,1-n-hexyloxy-3-methylbutyl), (13881, F, F, OMe, OMe,1-n-hexyloxy-2,2-dimethylpropyl), (B882, F, F, OMe, OMe,1-n-hexyloxyhexyl), (B883, F, F, OMe, OMe,1-n-hexyloxy-3,3-dimethylbutyl), (B884, F, F, OMe, OMe,1-n-hexyloxyheptyl), (B885, F, F, OMe, OMe, 1-n-hexyloxyoctyl), (B886,F, F, OMe, OMe, 1-n-hexyloxynonyl), (B887, F, F, OMe, OMe,1-n-hexyloxydecyl), (B888, F, F, OMe, OMe, 1-n-hexyloxyundecyl), (B889,F, F, OMe, OMe, 1-n-hexyloxydodecyl), (B890, F, F, OMe, OMe,1-n-hexyloxy-1-cyclohexylmethyl), (B891, F, F, OMe, OMe,3-isohexyloxypropyl), (B892, F, F, OMe, OMe,3-(3,3-dimethylbutyloxy)propyl), (B893, F, F, OMe, OMe,3-(2-cyclopentylethyloxy)propyl), (B894, F, F, OMe, OMe,1-n-octyloxyethyl), (B895, Cl, Cl, Me, F, 1-methyloxyethyl), (B898, Cl,Cl, Me, F, 1-methyloxybutyl), (B900, Cl, Cl, Me, F,1-methyloxy-2-methylpropyl), ('901, Cl, Cl, Me, F, 1-methyloxypentyl),(B902, Cl, Cl, Me, F, 1-methyloxy-3-methylbutyl), (B903, Cl, Cl, Me, F,3-methyloxy-3-methylbutyl), (B904, Cl, Cl, Me, F, 4-methyloxyhexyl),(B906, Cl, Cl, Me, F, 1-methyloxy-1-cyclohexylmethyl), (B907, Cl, Cl,Me, F, 1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B908, Cl, Cl, Me, F,1-ethyloxyethyl), (B909, Cl, Cl, Me, F, 1-ethyloxypropyl), (B910, Cl,Cl, Me, F, 1-ethyloxy-3-n-hexyloxypropyl), (B911, Cl, Cl, Me, F,1-ethyloxybutyl), (B912, Cl, Cl, Me, F, 1-ethyloxy-4-n-pentyloxybutyl),(B913, Cl, Cl, Me, F, 1-ethyloxy-2-methylpropyl), (B914, Cl, Cl, Me, F,1-ethyloxy-3-methylbutyl), (B915, Cl, Cl, Me, F, 1-ethyloxyhexyl),(B916, Cl, Cl, Me, F, 1-ethyloxyheptyl), (B3917, Cl, Cl, Me, F,1-ethyloxyoctyl), (B918, Cl, Cl, Me, F, 1-ethyloxynonyl), (B919, Cl, Cl,Me, F, 1-ethyloxydecyl), (B920, Cl, Cl, Me, F, 1-ethyloxyundecyl),(B921, Cl, Cl, Me, F, 1-ethyloxydodecyl), (B922, Cl, Cl, Me, F,1-ethyloxy-1-cyclohexylmethyl), (B923, Cl, Cl, Me, F,1-n-propyloxy-3-n-hexyloxypropyl), (B924, Cl, Cl, Me, F,1-n-propyloxy-4-n-pentyloxybutyl), (B925, Cl, Cl, Me, F,1-n-propyloxy-2-methylpropyl), (B926, Cl, Cl, Me, F,1-n-propyloxy-3-methylbutyl), (B928, Cl, Cl, Me, F, 1-n-propyloxyhexyl),(B929, Cl, Cl, Me, F, 1-n-propyloxy-3,3-dimethylbutyl), (B930, Cl, Cl,Me, F, 1-n-propyloxyheptyl), (B931, Cl, Cl, Me, F, 1-n-propyloxyoctyl),(B932, Cl, Cl, Me, F, 1-n-propyloxynonyl), (B933, Cl, Cl, Me, F,1-n-propyloxydecyl), (B934, Cl, Cl, Me, F, 1-n-propyloxyundecyl), (B935,Cl, Cl, Me, F, 1-n-propyloxydodecyl), (B937, Cl, Cl, Me, F,1-isopropyloxyethyl), (B938, Cl, Cl, Me, F, 1-isopropyloxypropyl),(B939, Cl, Cl, Me, F, 1-isopropyloxy-3-n-hexyloxypropyl), (B940, Cl, Cl,Me, F, 1-isopropyloxybutyl), (B941, Cl, Cl, Me, F,1-isopropyloxy-4-n-pentyloxybutyl), (B942, Cl, Cl, Me, F,1-isopropyloxy-2-methylpropyl), (B943, Cl, Cl, Me, F,1-isopropyloxypentyl), (B944, Cl, Cl, Me, F,1-isopropyloxy-3-methylbutyl), (B945, Cl, Cl, Me, F,1-isopropyloxy-2,2-dimethylpropyl), (B946, Cl, Cl, Me, F,1-isopropyloxyhexyl), (B947, Cl, Cl, Me, F,1-isopropyloxy-3,3-dimethylbutyl), (B948, Cl, Cl, Me, F,1-isopropyloxyheptyl), (B949, Cl, Cl, Me, F, 1-isopropyloxyoctyl),(B950, Cl, Cl, Me, F, 1-isopropyloxynonyl), (B951, Cl, Cl, Me, F,1-isopropyloxydecyl), (B952, Cl, Cl, Me, F, 1-isopropyloxyundecyl),(B953, Cl, Cl, Me, F, 1-isopropyloxydodecyl), (B954, Cl, Cl, Me, F,1-isopropyloxy-1-cyclohexylmethyl), (B955, Cl, Cl, Me, F,1,4-di(n-butyloxy)butyl), (B956, Cl, Cl, Me, F,1-n-butyloxy-2-methylpropyl), (B957, Cl, Cl, Me, F,1-n-butyloxy-3-methylbutyl), (B959, Cl, Cl, Me, F, 1-n-butyloxyhexyl),(B960, Cl, Cl, Me, F, 1-n-butyloxy-3,3-dimethylbutyl), (B961, Cl, Cl,Me, F, 1-n-butyloxyheptyl), (B962, Cl, Cl, Me, F, 1-n-butyloxyoctyl),(B963, Cl, Cl, Me, F, 1-n-butyloxynonyl), (B964, Cl, Cl, Me, F,1-n-butyloxydecyl), (B965, Cl, Cl, Me, F, 1-n-butyloxyundecyl), (B966,Cl, Cl, Me, F, 1-n-butyloxydodecyl), (B968, Cl, Cl, Me, F,1-isobutyloxyethyl), (B969, Cl, Cl, Me, F, 1-isobutyloxypropyl), (B970,Cl, Cl, Me, F, 1-isobutyloxybutyl), (B971, Cl, Cl, Me, F,1-isobutyloxy-2-methylpropyl), (3972, Cl, Cl, Me, F,1-isobutyloxypentyl), (B973, Cl, Cl, Me, F,1-isobutyloxy-3-methylbutyl), (B974, Cl, Cl, Me, F,1-isobutyloxy-2,2-dimethylpropyl), (B975, Cl, Cl, Me, F,1-isobutyloxyhexyl), (B976, Cl, Cl, Me, F,1-isobutyloxy-3,3-dimethylbutyl), (B977, Cl, Cl, Me, F,1-isobutyloxyheptyl), (B978, Cl, Cl, Me, F, 1-isobutyloxyoctyl), (B979,Cl, Cl, Me, F, 1-isobutyloxyynonyl), (B980, Cl, Cl, Me, F,1-isobutyloxydecyl), (B981, Cl, Cl, Me, F, 1-isobutyloxyundecyl), (B982,Cl, Cl, Me, F, 1-isobutyloxydodecyl), (13983, Cl, Cl, Me, F,1-isobutox-1-cyclohexylymethyl), (B984, Cl, Cl, Me, F,1-t-butyloxyethyl), (B985, Cl, Cl, Me, F, 1-t-butyloxypropyl), (B986,Cl, Cl, Me, F, 1-t-butyloxybutyl), (B987, Cl, Cl, Me, F,1-t-butyloxy-2-methylpropyl), (B988, Cl, Cl, Me, F, 1-t-butyloxypentyl),(B3989, Cl, Cl, Me, F, 1-t-butyloxy-3-methylbutyl), (B990, Cl, Cl, Me,F, 1-t-butyloxy-2,2-dimethylpropyl), (B991, Cl, Cl, Me, F,1-t-butyloxyhexyl), (B992, Cl, Cl, Me, F,1-t-butyloxy-3,3-dimethylbutyl), (B993, Cl, Cl, Me, F,1-t-butyloxyheptyl), (B994, Cl, Cl, Me, F, 1-t-butyloxyoctyl), (B995,Cl, Cl, Me, F, 1-t-butyloxynonyl), (B996, Cl, Cl, Me, F,1-t-butyloxydecyl), (B997, Cl, Cl, Me, F, 1-t-butyloxyundecyl), (B998,Cl, Cl, Me, F, 1-t-butyloxydodecyl), (B999, Cl, Cl, Me, F,1-t-butyloxy-1-cyclohexylmethyl), (B1000, Cl, Cl, Me, F,1-n-pentyloxyethyl), (B1001, Cl, Cl, Me, F,1-n-pentyloxy-2-methylpropyl), (B1002, Cl, Cl, Me, F,1-n-pentyloxy-3-methylbutyl), (B1003, Cl, Cl, Me, F,1-n-pentyloxy-2,2-dimethylpropyl), (B1004, Cl, Cl, Me, F,1-n-pentyloxyhexyl), (B1005, Cl, Cl, Me, F,1-n-pentyloxy-3,3-dimethylbutyl), (B1006, Cl, Cl, Me, F,1-n-pentyloxyheptyl), (B1007, Cl, Cl, Me, F, 1-n-pentyloxyoctyl),(B1008, Cl, Cl, Me, F, 1-n-pentyloxynonyl), (B1009, Cl, Cl, Me, F,1-n-pentyloxydecyl), (B1010, Cl, Cl, Me, F, 1-n-pentyloxyundecyl),(B1011, Cl, Cl, Me, F, 1-n-pentyloxydodecyl), (B1012, Cl, Cl, Me, F,1-n-pentyloxy-1-cyclohexylmethyl), (B1013, Cl, Cl, Me, F,1-neopentyloxyethyl), (B1014, Cl, Cl, Me, F, 1-neopentyloxypropyl),(B1015, Cl, Cl, Me, F, 1-neopentyloxybutyl), (B1016, Cl, Cl, Me, F,1-neopentyloxy-2-methylpropyl), (B11017, Cl, Cl, Me, F,1-neopentyloxypentyl), (B1018, Cl, Cl, Me, F,1-neopentyloxy-3-methylbutyl), (B1019, Cl, Cl, Me, F,1-neopentyloxy-2,2-dimethylpropyl), (B1020, Cl, Cl, Me, F,1-neopentyloxyhexyl), (B1021, Cl, Cl, Me, F,1-neopentyloxy-3,3-dimethylbutyl), (B1022, Cl, Cl, Me, —F,1-neopentyloxyheptyl), (B1023, Cl, Cl, Me, F, 1-neopentyloxyoctyl),(B1024, Cl, Cl, Me, F, 1-neopentyloxynonyl), (B1025, Cl, Cl, Me, F,1-neopentyloxydecyl), (B1026, Cl, Cl, Me, F, 1-neopentyloxyundecyl),(B1027, Cl, Cl, Me, F, 1-neopentyloxydodecyl), (B1028, Cl, Cl, Me, F,1-neopentyloxy-1-cyclohexylmethyl), (B1029, Cl, Cl, Me, F,1-n-hexyloxybutyl), (B1030, Cl, Cl, Me, F, 1-n-hexyloxy-2-methylpropyl),(B1031, Cl, Cl, Me, F, 1-n-hexyloxypentyl), (B1032, Cl, Cl, Me, F,1-n-hexyloxy-3-methylbutyl), (B1033, Cl, Cl, Me, F,1-n-hexyloxy-2,2-dimethylpropyl), (B1034, Cl, Cl, Me, F,1-n-hexyloxyhexyl), (B1035, Cl, Cl, Me, F,1-n-hexyloxy-3,3-dimethylbutyl), (B1036, Cl, Cl, Me, F,1-n-hexyloxyheptyl), (B1037, Cl, Cl, Me, F, 1-n-hexyloxyoctyl), (B1038,Cl, Cl, Me, F, 1-n-hexyloxynonyl), (B1039, Cl, Cl, Me, F,1-n-hexyloxydecyl), (B1040, Cl, Cl, Me, F, 1-n-hexyloxyundecyl), (B1041,Cl, Cl, Me, F, 1-n-hexyloxydodecyl), (B1042, Cl, Cl, Me, F,1-n-hexyloxy-1-cyclohexylmethyl), (B1043, Cl, Cl, Me, OMe,1-methyloxyethyl), (B1044, Cl, Cl, Me, OMe, 1-methyloxypropyl), (B1045,Cl, Cl, Me, OMe, 1-methyloxy-3-n-hexyloxypropyl), (B1046, Cl, Cl, Me,OMe, 1-methyloxybutyl), (B1047, Cl, Cl, Me, OMe,1-methyloxy-4-n-pentyloxybutyl), (B1048, Cl, Cl, Me, OMe,1-methyloxy-2-methylpropyl), (B1149, Cl, Cl, Me, OMe,1-methyloxypentyl), (B1050, Cl, Cl, Me, OMe, 1-methyloxy-3-methylbutyl),(B1051, Cl, Cl, Me, OMe, 1-methyloxy-2,2-dimethylpropyl), (B1052, Cl,Cl, Me, OMe, 1-methyloxyhexyl), (B1055, Cl, Cl, Me, OMe,1-methyloxyheptyl), (B1056, Cl, Cl, Me, OMe, 1-methyloxyoctyl), (B1057,Cl, Cl, Me, OMe, 3-methyloxyoctyl), (B1058, Cl, Cl, Me, OMe,1-methyloxynonyl), (B1061, Cl, Cl, Me, OMe, 1-methyloxydodecyl), (B1062,Cl, Cl, Me, OMe, 1-methyloxy-1-cyclohexylmethyl), (B1063, Cl, Cl, Me,OMe, 1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B1064, Cl, Cl, Me,OMe, 1-ethyloxyethyl), (B1065, Cl, Cl, Me, OMe, 1-ethyloxypropyl),(B1066, Cl, Cl, Me, OMe, 1-ethyloxy-3-n-hexyloxypropyl), (B1067, Cl, Cl,Me, OMe, 1-(4-ethyloxybutyloxy)propyl), (B1068, Cl, Cl, Me, OMe,1-ethyloxybutyl), (B1069, Cl, Cl, Me, OMe,1-ethyloxy-4-n-pentyloxybutyl), (B1070, Cl, Cl, Me, OMe,1-ethyloxy-2-methylpropyl), (B1071, Cl, Cl, Me, OMe, 1-ethyloxypentyl),(B11072, Cl, Cl, Me, OMe, 1-ethyloxy-3-methylbutyl), (B1073, Cl, Cl, Me,OMe, 1-ethyloxy-2,2-dimethylpropyl), (B1074, Cl, Cl, Me, OMe,1-ethyloxyhexyl), (B1375, Cl, Cl, Me, OMe,1-ethyloxy-3,3-dimethylbutyl), (B1076, Cl, Cl, Me, OMe,1-ethyloxyheptyl), (B1077, Cl, Cl, Me, OMe, 1-ethyloxyoctyl), (B1078,Cl, Cl, Me, OMe, 1-ethyloxynonyl), (1B1079, Cl, Cl, Me, OMe,1-ethyloxydecyl), (B1080, Cl, Cl, Me, OMe, 1-ethyloxyundecyl), (B1081,Cl, Cl, Me, OMe, 1-ethyloxydodecyl), (B1082, Cl, Cl, Me, OMe,1-ethyloxy-1-cyclohexylmethyl), (B1083, Cl, Cl, Me, OMe,1-n-propyloxyethyl), (B1084, Cl, Cl, Me, OMe, 1-n-propyloxypropyl),(B1085, Cl, Cl, Me, OMe, 3-n-propyloxypropyl), (B1086, Cl, Cl, Me, OMe,1-n-propyloxy-3-n-hexyloxypropyl), (B1087, Cl, Cl, Me, OMe,1-n-propyloxybutyl), (B1088, Cl, Cl, Me, OMe,1-n-propyloxy-4-n-pentyloxybutyl), (B1089, Cl, Cl, Me, OMe,1,4-di(n-propyloxy)butyl), (B11090, Cl, Cl, Me, OMe,1-n-propyloxy-2-methylpropyl), (B1091, Cl, Cl, Me, OMe,1-n-propyloxypentyl), (131092, Cl, Cl, Me, OMe,1-n-propyloxy-3-methylbutyl), (B1093, Cl, Cl, Me, OMe,1-n-propyloxy-2,2-dimethylpropyl), (B1094, Cl, Cl, Me, OMe,1-n-propyloxyhexyl), (B11095, Cl, Cl, Me, OMe,1-n-propyloxy-3,3-dimethylbutyl), (B31096, Cl, Cl, Me, OMe,1-n-propyloxyheptyl), (B1097, Cl, Cl, Me, OMe, 1-n-propyloxyoctyl),(B1098, Cl, Cl, Me, OMe, 1-n-propyloxynonyl), (B11099, Cl, Cl, Me, OMe,1-n-propyloxydecyl), (B1100, Cl, Cl, Me, OMe, 1-n-propyloxyundecyl),(B1100, Cl, Cl, Me, OMe, 1-n-propyloxydodecyl), (B1103, Cl, Cl, Me, OMe,1-isopropyloxyethyl), (B1104, Cl, Cl, Me, OMe, 1-isopropyloxypropyl),(B1105, Cl, Cl, Me, OMe, 3-isopropyloxypropyl), (B1106, Cl, Cl, Me, OMe,1-isopropyloxy-3-n-hexyloxypropyl), (B1107, Cl, Cl, Me, OMe,1-isopropyloxybutyl), (B1108, Cl, Cl, Me, OMe,1-isopropyloxy-4-n-pentyloxybutyl), (B1109, Cl, Cl, Me, OMe,1-isopropyloxy-2-methylpropyl), (B1110, Cl, Cl, Me, OMe,1-isopropyloxypentyl), (B1111, Cl, Cl, Me, OMe,1-isopropyloxy-3-methylbutyl), (B1112, Cl, Cl, Me, OMe,1-isopropyloxy-2,2-dimethylpropyl), (B1113, Cl, Cl, Me, OMe,1-isopropyloxyhexyl), (B1114, Cl, Cl, Me, OMe,1-isopropyloxy-3,3-dimethylbutyl), (B1115, Cl, Cl, Me, OMe,1-isopropyloxyheptyl), (B1116, Cl, Cl, Me, OMe, 1-isopropyloxyoctyl),(B1117, Cl, Cl, Me, OMe, 1-isopropyloxynonyl), (B1118, Cl, Cl, Me, OMe,1-isopropyloxydecyl), (B1119, Cl, Cl, Me, OMe, 1-isopropyloxyundecyl),(B1120, Cl, Cl, Me, OMe, 1-isopropyloxydodecyl), (B1121, Cl, Cl, Me,OMe, 1-isopropyloxy-1-cyclohexylmethyl), (B1123, Cl, Cl, Me, OMe,1-n-butyloxypropyl), (B1125, Cl, Cl, Me, OMe, 1,4-di(n-butyloxy)butyl),(B1126, Cl, Cl, Me, OMe, 1-n-butyloxybutyl), (B1127, Cl, Cl, Me, OMe,1-n-butyloxy-2-methylpropyl), (B1128, Cl, Cl, Me, OMe,1-n-butyloxypentyl), (B1129, Cl, Cl, Me, OMe,1-n-butyloxy-3-methylbutyl), (B1130, Cl, Cl, Me, OMe,1-n-butyloxy-2,2-dimethylpropyl), (B1131, Cl, Cl, Me, OMe,1-n-butyloxyhexyl), (B1132, Cl, Cl, Me, OMe,1-n-butyloxy-3,3-dimethylbutyl), (B1133, Cl, Cl, Me, OMe,1-n-butyloxyheptyl), (B1134, Cl, Cl, Me, OMe, 1-n-butyloxyoctyl),(B1135, Cl, Cl, Me, OMe, 1-n-butyloxynonyl), (B1136, Cl, Cl, Me, OMe,1-n-butyloxydecyl), (B1137, Cl, Cl, Me, OMe, 1-n-butyloxyundecyl),(B1138, Cl, Cl, Me, OMe, 1-n-butyloxydodecyl), (B1139, Cl, Cl, Me, OMe,1-n-butyloxy-1-cyclohexylmethyl), (B1140, Cl, Cl, Me, OMe,1-isobutyloxyethyl), (B1141, Cl, Cl, Me, OMe, 1-isobutyloxypropyl),(B1142, Cl, Cl, Me, OMe, 1-isobutyloxybutyl), (B1143, Cl, C—, Me, OMe,1-isobutyloxy-2-methylpropyl), (B1144, Cl, Cl, Me, OMe,1-isobutyloxypentyl), (B1145, Cl, Cl, Me, OMe,1-isobutyloxy-3-methylbutyl), (B1146, Cl, Cl, Me, OMe,1-isobutyloxy-2,2-dimethylpropyl), (B1147, Cl, Cl, Me, OMe,1-isobutyloxyhexyl), (B1148, Cl, Cl, Me, OMe,1-isobutyloxy-3,3-dimethylbutyl), (B1149, Cl, Cl, Me, OMe,1-isobutyloxyheptyl), (B1150, Cl, Cl, Me, OMe, 1-isobutyloxyoctyl),(B1151, Cl, Cl, Me, OMe, 1-isobutyloxyynonyl), (B1152, Cl, Cl, Me, OMe,1-isobutyloxydecyl), (B1153, Cl, Cl, Me, OMe, 1-isobutyloxyundecyl),(B1154, Cl, Cl, Me, OMe, 1-isobutyloxydodecyl), (B1155, Cl, Cl, Me, OMe,1-isobutyloxy-1-cyclohexylmethyl), (B1156, Cl, Cl, Me, OMe,1-t-butyloxyethyl), (B1157, Cl, Cl, Me, OMe, 1-t-butyloxypropyl),(B1158, Cl, Cl, Me, OMe, 1-t-butyloxybutyl), (B1159, Cl, Cl, Me, OMe,1-t-butyloxy-2-methylpropyl), (B1160, Cl, Cl, Me, OMe,1-t-butyloxypentyl), (B1161, Cl, Cl, Me, OMe,1-t-butyloxy-3-methylbutyl), (B1162, Cl, Cl, Me, OMe,1-t-butyloxy-2,2-dimethylpropyl), (B1163, Cl, Cl, Me, OMe,1-t-butyloxyhexyl), (B1164, Cl, Cl, Me, OMe,1-t-butyloxy-3,3-dimethylbutyl), (B1165, Cl, Cl, Me, OMe,1-t-butyloxyheptyl), (B1166, Cl, Cl, Me, OMe, 1-t-butyloxyoctyl),(B1167, Cl, Cl, Me, OMe, 1-t-butyloxynonyl), (B1168, Cl, Cl, Me, OMe,1-t-butyloxydecyl), (B1169, Cl, Cl, Me, OMe, 1-t-butyloxyundecyl),(B1170, Cl, Cl, Me, OMe, 1-t-butyloxydodecyl), (B1171, Cl, Cl, Me, OMe,1-t-butyloxy-1-cyclohexylmethyl), (B1172, Cl, Cl, Me, OMe,1-n-pentyloxyethyl), (B1173, Cl, Cl, Me, OMe, 1-n-pentyloxypropyl),(B1174, Cl, Cl, Me, OMe, 3-n-pentyloxypropyl), (B1175, Cl, Cl, Me, OMe,1-n-pentyloxy-3-methylthiopropyl), (B13116, Cl, Cl, Me, OMe,1-n-pentyloxybutyl), (B1177, Cl, Cl, Me, OMe,1-n-pentyloxy-2-methylpropyl), (B1178, Cl, Cl, Me, OMe,1-n-pentyloxypentyl), (B1179, Cl, Cl, Me, OMe,1-n-pentyloxy-3-methylbutyl), (B1180, Cl, Cl, Me, OMe,1-n-pentyloxy-2,2-dimethylpropyl), (B1181, Cl, Cl, Me, OMe,1-n-pentyloxyhexyl), (B1182, Cl, Cl, Me, OMe,1-n-pentyloxy-3,3-dimethylbutyl), (B1183, Cl, Cl, Me, OMe,1-n-pentyloxyheptyl), (B1184, Cl, Cl, Me, OMe, 1-n-pentyloxyoctyl),(B1185, Cl, Cl, Me, OMe, 1-n-pentyloxynonyl), (B1186, Cl, Cl, Me, OMe,1-n-pentyloxydecyl), (B1187, Cl, Cl, Me, OMe, 1-n-pentyloxyundecyl),(B1188, Cl, Cl, Me, OMe, 1-n-pentyloxydodecyl), (B1189, Cl, Cl, Me, OMe,1-n-pentyloxy-1-cyclohexylmethyl), (B1190, Cl, Cl, Me, OMe,1-isopentyloxypropyl), (B1191, Cl, Cl, Me, OMe, 1-neopentyloxyethyl),(B1192, Cl, Cl, Me, OMe, 1-neopentyloxypropyl), (B1193, Cl, Cl, Me, OMe,3-neopentyloxypropyl), (B1194, Cl, Cl, Me, OMe, 1-neopentyloxybutyl),(B1195, Cl, Cl, Me, OMe, 1-neopentyloxy-2-methylpropyl), (B1196, Cl, Cl,Me, OMe, 1-neopentyloxypentyl), (B1197, Cl, Cl, Me, OMe,1-neopentyloxy-3-methylbutyl), (B1198, Cl, Cl, Me, OMe,1-neopentyloxy-2,2-dimethylpropyl), (B1199, Cl, Cl, Me, OMe,1-neopentyloxyhexyl), (B1200, Cl, Cl, Me, OMe,1-neopentyloxy-3,3-dimethylbutyl), (B1201, Cl, Cl, Me, OMe,1-neopentyloxyheptyl), (B202, Cl, Cl, Me, OMe, 1-neopentyloxyoctyl),(B1203, Cl, Cl, Me, OMe, 1-neopentyloxynonyl), (B1204, Cl, Cl, Me, OMe,1-neopentyloxydecyl), (B1205, Cl, Cl, Me, OMe, 1-neopentyloxyundecyl),(B1206, Cl, Cl, Me, OMe, 1-neopentyloxydodecyl), (B1207, Cl, Cl, Me,OMe, 1-neopentyloxy-1-cyclohexylmethyl), (B1208, Cl, Cl, Me, OMe,1-n-hexyloxyethyl), (B1209, Cl, Cl, Me, OMe, 1-n-hexyloxypropyl),(B1210, Cl, Cl, Me, OMe, 3-n-hexyloxypropyl), (B1211, Cl, Cl, Me, OMe,1-n-hexyloxybutyl), (B1212, Cl, Cl, Me, OMe,1-n-hexyloxy-2-methylpropyl), (B1213, Cl, Cl, Me, OMe,1-n-hexyloxypentyl), (B1214, Cl, Cl, Me, OMe,1-n-hexyloxy-3-methylbutyl), (B1215, Cl, Cl, Me, OMe,1-n-hexyloxy-2,2-dimethylpropyl), (B1216, Cl, Cl, Me, OMe,1-n-hexyloxyhexyl), (B1217, Cl, Cl, Me, OMe,1-n-hexyloxy-3,3-dimethylbutyl), (B1218, Cl, Cl, Me, OMe,1-n-hexyloxyheptyl), (B1219, Cl, Cl, Me, OMe, 1-n-hexyloxyoctyl),(B1220, Cl, Cl, Me, OMe, 1-n-hexyloxynonyl), (B1221, Cl, Cl, Me, OMe,1-n-hexyloxydecyl), (B1222, Cl, Cl, Me, OMe, 1-n-hexyloxyundecyl),(B1223, Cl, Cl, Me, OMe, 1-n-hexyloxydodecyl), (B1224, Cl, Cl, Me, OMe,1-n-hexyloxy-1-cyclohexylmethyl), (B1225, Cl, Cl, Me, OMe,3-isohexyloxydodecyl), (B1226, Cl, Cl, Me, OMe,3-(3,3-dimethylbutyloxy)propyl), (B1227, Cl, Cl, Me, OMe,3-(2-cyclopentylethyloxy)propyl), (B13228, Cl, Cl, Me, OMe,1-n-octyloxydodecyl), (B1229, Cl, Cl, OMe, F, 1-methyloxyethyl), (B1230,Cl, Cl, OMe, F, 1-methyloxypropyl), (B1231, Cl, Cl, OMe, F,1-methyloxy-3-n-hexyloxypropyl), (B1232, Cl, Cl, OMe, F,1-methyloxybutyl), (B1233, Cl, Cl, OMe, F,1-methyloxy-4-n-pentyloxybutyl), (B1234, Cl, Cl, OMe, F,1-methyloxy-2-methylpropyl), (B1235, Cl, Cl, OMe, F, 1-methyloxypentyl),(B1236, Cl, Cl, OMe, F, 1-methyloxy-3-methylbutyl), (B1237, Cl, Cl, OMe,F, 1-methyloxy-2,2-dimethylpropyl), (B1239, Cl, Cl, OMe, F,4-methyloxyhexyl), (11240, Cl, Cl, OMe, F, 1-methyloxy-4-methylpentyl),(B1241, Cl, Cl, OMe, F, 1-methyloxy-3,3-dimethylbutyl), (B1242, Cl, Cl,OMe, F, 3-methyloxy-2,4-dimethyl-3-pentyl), (B1243, Cl, Cl, OMe, F,1-methyloxyheptyl), (B1244, Cl, Cl, OMe, F, 4-methyloxy-4-heptyl),(B1245, Cl, Cl, OMe, F, 1-methyloxyoctyl), (B1246, Cl, Cl, OMe, F,3-methyloxyoctyl), (B1247, Cl, Cl, OMe, F, 1-methyloxynonyl), (B1248,Cl, Cl, OMe, F, 1-methyloxydecyl), (B1249, Cl, Cl. OMe, F,1-methyloxyundecyl), (B1251, Cl, Cl, OMe, F,1-methyloxy-1-cyclohexylmethyl), (B1252, Cl, Cl, OMe, F,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B1253, Cl, Cl, OMe, F,1-ethyloxyethyl), (B1254, Cl, Cl, OMe, F, 1-ethyloxypropyl), (B1255, Cl,Cl, OMe, F, 1-ethyloxy-3-n-hexyloxypropyl), (B1256, Cl, Cl, OMe, F,1-(4-ethyloxybutyloxy)propyl), (B1257, Cl, Cl, OMe, F, 1-ethyloxybutyl),(B1258, Cl, Cl, OMe, F, 1-ethyloxy-4-n-pentyloxybutyl), (B1259, Cl, Cl,OMe, F, 1-ethyloxy-2-methylpropyl), (B1260, Cl, Cl, OMe, F,1-ethyloxypentyl), (B1261, Cl, Cl, OMe, F, 1-ethyloxy-3-methylbutyl),(B1262, Cl, Cl, OMe, F, 1-ethyloxy-2,2-dimethylpropyl), (B1263, Cl, Cl,OMe, F, 1-ethyloxyhexyl), (B1264, Cl, Cl, OMe, F,1-ethyloxy-3,3-dimethylbutyl), (B1265, Cl, Cl, OMe, F,1-ethyloxyheptyl), (B1266, Cl, Cl, OMe, F, 1-ethyloxyoctyl), (B1267, Cl,Cl, OMe, F, 1-ethyloxynonyl), (B1268, Cl, Cl, OMe, F, 1-ethyloxydecyl),(B1269, Cl, Cl, OMe, F, 1-ethyloxyundecyl), (B1270, Cl, Cl, OMe, F,1-ethyloxydodecyl), (B1271, Cl, Cl, OMe, F,1-ethyloxy-1-cyclohexylmethyl), (B1272, Cl, Cl, OMe, F,1-n-propyloxyethyl), (B1273, Cl, Cl, OMe, F, 1-n-propyloxypropyl),(B1274, Cl, Cl, OMe, F, 3-n-propyloxypropyl), (B1275, Cl, Cl, OMe, F,1-n-propyloxy-3-n-hexyloxypropyl), (B1276, Cl, Cl, OMe, F,1-n-propyloxybutyl), (B1277, Cl, Cl, OMe, F,1-n-propyloxy-4-n-pentyloxybutyl), (B1278, Cl, Cl, OMe, F,1,4-di(n-propyloxy)butyl), (B1279, Cl, Cl, OMe, F,1-n-propyloxy-2-methylpropyl), (B1280, Cl, Cl, OMe, F,1-n-propyloxypentyl), (B1281, Cl, Cl, OMe, F,1-n-propyloxy-3-methylbutyl), (B1282, Cl, Cl, OMe, F,1-n-propyloxy-2,2-dimethylpropyl), (B1283, Cl, Cl, OMe, F,1-n-propyloxyhexyl), (B1284, Cl, Cl, OMe, F,1-n-propyloxy-3,3-dimethylbutyl), (B1285, Cl, Cl, OMe, F,1-n-propyloxyheptyl), (B1286, Cl, Cl, OMe, F, 1-n-propyloxyoctyl),(B1287, Cl, Cl, OMe, F, 1-n-propyloxynonyl), (B1288, Cl, Cl, OMe, F,1-n-propyloxydecyl), (B1289, Cl, Cl, OMe, F, 1-n-propyloxyundecyl),(B1290, Cl, Cl, OMe, F, 1-n-propyloxydodecyl), (B1291, Cl, Cl, OMe, F,1-n-propyloxy-1-cyclohexylmethyl), (B1292, Cl, Cl, OMe, F,1-isopropyloxyethyl), (B1293, Cl, Cl, OMe, F, 1-isopropyloxypropyl),(B1294, Cl, Cl, OMe, F, 3-isopropyloxypropyl), (31295, Cl, Cl, OMe, F,1-isopropyloxy-3-n-hexyloxypropyl), (B1296, Cl, Cl, OMe, F,1-isopropyloxybutyl), (B1297, Cl, Cl, OMe, F,1-isopropyloxy-4-n-pentyloxybutyl), (B1298, Cl, Cl, OMe, F,1-isopropyloxy-2-methylpropyl), (B1299, Cl, Cl. OMe, ° F.,1-isopropyloxypentyl), (B1300, Cl, Cl, OMe, F,1-isopropyloxy-3-methylbutyl), (B1301, Cl, Cl, OMe, F,1-isopropyloxy-2,2-dimethylpropyl), (B1302, Cl, Cl, OMe, F,1-isopropyloxyhexyl), (B1303, Cl, Cl, OMe, F,1-isopropyloxy-3,3-dimethylbutyl), (B1304, Cl, Cl, OMe, F,1-isopropyloxyheptyl), (B1305, Cl, Cl, OMe, F, 1-isopropyloxyoctyl),(B1306, Cl, Cl, OMe, F, 1-isopropyloxynonyl), (B31307, Cl, Cl, OMe, F,1-isopropyloxydecyl), (B1308, Cl, Cl, OMe, F, 1-isopropyloxyundecyl),(B1309, Cl, Cl, OMe, F, 1-isopropyloxydodecyl), (B1310, Cl, Cl, OMe, F,1-isopropyloxy-1-cyclohexylmethyl), (B1311, Cl, Cl, OMe, F,1-n-butyloxyethyl), (B1312, Cl, Cl, OMe, F, 1-n-butyloxypropyl), (B1313,Cl, Cl, OMe, F, 3-n-butyloxypropyl), (B1314, Cl, Cl, OMe, F,1-n-butyloxybutyl), (B1315, Cl, Cl, OMe, F, 1,4-di(n-butyloxy)butyl),(B1316, Cl, Cl, OMe, F, 1-n-butyloxy-2-methylpropyl), (B1317, Cl, Cl,OMe, F, 1-n-butyloxypentyl), (B1318, Cl, Cl, OMe, F,1-n-butyloxy-3-methylbutyl), (B11319, Cl, Cl, OMe, F,1-n-butyloxy-2,2-dimethylpropyl), (B1320, Cl, Cl, OMe, F,1-n-butyloxyhexyl), (B1321, Cl, Cl, OMe, F,1-n-butyloxy-3,3-dimethylbutyl), (B1322, Cl, Cl, OMe, F,1-n-butyloxyheptyl), (B1323, Cl, Cl, OMe, F, 1-n-butyloxyoctyl), (B1324,Cl, Cl, OMe, F, 1-n-butyloxynonyl), (B1325, Cl, Cl, OMe, F,1-n-butyloxydecyl), (B1326, Cl, Cl, OMe, F, 1-n-butyloxyundecyl),(B1327, Cl, Cl, OMe, F, 1-n-butyloxydodecyl), (B1328, Cl, Cl, OMe, F,1-n-butyloxy-1-cyclohexylmethyl), (B1329, Cl, Cl, OMe, F,1-isobutyloxyethyl), (B1330, Cl, Cl, OMe, F, 1-isobutyloxypropyl),(B1331, Cl, Cl, OMe, F, 1-isobutyloxybutyl), (B1332, Cl, Cl, OMe, F,1-isobutyloxy-2-methylpropyl), (B1333, Cl, Cl, OMe, F,1-isobutyloxypentyl), (B1334, Cl, Cl, OMe, F,1-isobutyloxy-3-methylbutyl), (B1335, Cl, Cl, OMe, F,1-isobutyloxy-2,2-dimethylpropyl), (B1336, Cl, Cl, OMe, F,1-isobutyloxyhexyl), (B1337, Cl, Cl, OMe, F,1-isobutyloxy-3,3-dimethylbutyl), (B1338, Cl, Cl, OMe, F,1-isobutyloxyheptyl), (B1339, Cl, Cl, OMe, F, 1-isobutyloxyoctyl),(B11340, Cl, Cl, OMe, F, 1-isobutyloxyynonyl), (B1341, Cl, Cl, OMe, F,1-isobutyloxydecyl), (B1342, Cl, Cl, OMe, F, 1-isobutyloxyundecyl),(B1343, Cl, Cl, OMe, F, 1-isobutyloxydodecyl), (B1344, Cl, Cl, OMe, F,1-isobutyloxy-1-cyclohexylmethyl), (B1345, Cl, Cl, OMe, F,1-t-butyloxyethyl), (B1346, Cl, Cl, OMe, F, 1-t-butyloxypropyl), (B1347,Cl, Cl, OMe, F, 1-t-butyloxybutyl), (B1348, Cl, Cl, OMe, F,1-t-butyloxy-2-methylpropyl), (B1349, Cl, Cl, OMe, F,1-t-butyloxypentyl), (B1350, Cl, Cl, OMe, F,1-t-butyloxy-3-methylbutyl), (B1351, Cl, Cl, OMe, F,1-t-butyloxy-2,2-dimethylpropyl), (B1352, Cl, Cl, OMe, F,1-t-butyloxyhexyl), (B1353, Cl, Cl, OMe, F,1-t-butyloxy-3,3-dimethylbutyl), (B1354, Cl, Cl, OMe, F,1-t-butyloxyheptyl), (B1355, Cl, Cl, OMe, F, 1-t-butylbxyoctyl), (B1356,Cl, Cl, OMe, F, 1-t-butyloxynonyl), (B1357, Cl, Cl, OMe, F,1-t-butyloxydecyl), (B1358, Cl, Cl, OMe, F, 1-t-butyloxyundecyl),(B1359, Cl, Cl, OMe, F, 1-t-butyloxydodecyl), (B1360, Cl, Cl, OMe, F,1-t-butyloxy-1-cyclohexylmethyl), (B1361, Cl, Cl, OMe, F,1-n-pentyloxyethyl), (B1362, Cl, Cl, OMe, F, 1-n-pentyloxypropyl),(B1363, Cl, Cl, OMe, F, 3-n-pentyloxypropyl), (B1364, Cl, Cl, OMe, F,1-n-pentyloxy-3-methylthiopropyl), (B1365, Cl, Cl, OMe, F,1-n-pentyloxybutyl), (B3166, Cl, Cl, OMe, F,1-n-pentyloxy-2-methylpropyl), (B1367, Cl, Cl, OMe, F,1-n-pentyloxypentyl), (B1368, Cl, Cl, OMe, F,1-n-pentyloxy-3-methylbutyl), (B1369, Cl, Cl, OMe, F,1-n-pentyloxy-2,2-dimethylpropyl), (B1370, Cl, Cl, OMe, F,1-n-pentyloxyhexyl), (B1371, Cl, Cl, OMe, F,1-n-pentyloxy-3,3-dimethylbutyl), (B1372, Cl, Cl, OMe, F,1-n-pentyloxyheptyl), (B1373, Cl, Cl, OMe, F, 1-n-pentyloxyoctyl),(B1374, Cl, Cl, OMe, F, 1-n-pentyloxynonyl), (B1375, Cl, Cl, OMe, F,1-n-pentyloxydecyl), (B1376, Cl, Cl, OMe, F, 1-n-pentyloxyundecyl),(B1377, Cl, Cl, OMe, F, 1-n-pentyloxydodecyl), (B1378, Cl, Cl, OMe, F,1-n-pentyloxy-1-cyclohexylmethyl), (B1379, Cl, Cl, OMe, F,1-isopentyloxypropyl), (B1380, Cl, Cl, OMe, F, 1-neopentyloxyethyl),(B1381, Cl, Cl, OMe, F, 1-neopentyloxypropyl), (B1382, Cl, Cl, OMe, F,3-neopentyloxypropyl), (B1383, Cl, Cl, OMe, F, 1-neopentyloxybutyl),(B1384, Cl, Cl, OMe, F, 1-neopentyloxy-2-methylpropyl), (B1385, Cl, Cl,OMe, F, 1-neopentyloxypentyl), (B1386, Cl, Cl, OMe, F,1-neopentyloxy-3-methylbutyl), (B1387, Cl, Cl, OMe, F,1-neopentyloxy-2,2-dimethylpropyl), (B1388, Cl, Cl, OMe, F,1-neopentyloxyhexyl), (B1389, Cl, Cl, OMe, F,1-neopentyloxy-3,3-dimethylbutyl), (B1390, Cl, Cl, OMe, F,1-neopentyloxyheptyl), (B1391, Cl, Cl, OMe, F, 1-neopentyloxyoctyl),(B1392, Cl, Cl, OMe, F, 1-neopentyloxynonyl), (B1393, Cl, Cl, OMe, F,1-neopentyloxydecyl), (B1394, Cl, Cl, OMe, F, 1-neopentyloxyundecyl),(B1395, Cl, Cl, OMe, F, 1-neopentyloxydodecyl), (B1396, Cl, Cl, OMe, F,1-neopentyloxy-1-cyclohexylmethyl), (B1397, Cl, Cl, OMe, F,1-n-hexyloxyethyl), (B1398, Cl, Cl, OMe, F, 1-n-hexyloxypropyl), (B1399,Cl, Cl, OMe, F, 3-n-hexyloxypropyl), (131400, Cl, Cl, OMe, F,1-n-hexyloxybutyl), (1314, Cl, Cl, OMe, F, 1-n-hexyloxy-2-methylpropyl),(B1402, Cl, Cl, OMe, F, 1-n-hexyloxypentyl), (B1403, Cl, Cl, OMe, F,1-n-hexyloxy-3-methylbutyl), (B1404, Cl, Cl, OMe, F,1-n-hexyloxy-2,2-dimethylpropyl), (B1405, Cl, Cl, OMe, F,1-n-hexyloxyhexyl), (B1406, Cl, Cl, OMe, F,1-n-hexyloxy-3,3-dimethylbutyl), (B1407, Cl, Cl, OMe, F,1-n-hexyloxyheptyl), (B1408, Cl, Cl, OMe, F, 1-n-hexyloxyoctyl), (B1409,Cl, Cl, OMe, F, 1-n-hexyloxynonyl), (B1410, Cl, Cl, OMe, F,1-n-hexyloxydecyl), (B1411, Cl, Cl, OMe, F, 1-n-hexyloxyundecyl),(B1412, Cl, Cl, OMe, F, 1-n-hexyloxydodecyl), (B1413, Cl, Cl, OMe, F,1-n-hexyloxy-1-cyclohexylmethyl), (B1414, Cl, Cl, OMe, F,3-isohexyloxypropyl), (B1415, Cl, Cl, OMe, F,3-(3,3-dimethylbutyloxy)propyl), (B1416, Cl, Cl, OMe, F,3-(2-cyclopentylethoxy)propyl), (B1417, Cl, Cl, OMe, F,1-n-octyloxyethyl), (B1418, Cl, Cl, OMe, OMe, 1-methyloxyethyl), (B1419,Cl, Cl, OMe, OMe, 1-methyloxypropyl), (B1420, Cl, Cl, OMe, OMe,1-methyloxy-3-n-hexyloxypropyl), (B1421, Cl, Cl, OMe, OMe,1-methyloxybutyl), (B1422, Cl, Cl, OMe, OMe,1-methyloxy-4-n-pentyloxybutyl), (B1423, Cl, Cl, OMe, OMe,1-methyloxy-2-methylpropyl), (B1424, Cl, Cl, OMe, OMe,1-methyloxypentyl), (B1425, Cl, Cl, OMe, OMe,1-methyloxy-3-methylbutyl), (B1426, Cl, Cl, OMe, OMe,1-methyloxy-2,2-dimethylpropyl), (B1427, Cl, Cl, OMe, OMe,1-methyloxyhexyl), (B1428, Cl, Cl, OMe, OMe, 4-methyloxyhexyl), (B1429,Cl, Cl, OMe, OMe, 1-methyloxy-4-methylpentyl), (B1430, Cl, Cl, OMe, OMe,1-methyloxy-3,3-dimethylbutyl), (B1431, Cl, Cl, OMe, OMe,3-methyloxy-2,4-dimethyl-3-pentyl), (B1432, Cl, Cl, OMe, OMe,1-methyloxyheptyl), (B1433, Cl, Cl, OMe, OMe, 4-methyloxy-4-heptyl),(B1434, Cl, Cl, OMe, OMe, 1-methyloxyoctyl), (B1435, Cl, Cl, OMe, OMe,3-methyloxyoctyl), (B1436, Cl, Cl, OMe, OMe, 1-methyloxynonyl), (B1437,Cl, Cl, OMe, OMe, 1-methyloxydecyl), (B1439, Cl, Cl, OMe, OMe,1-methyloxydodecyl), (B1440, Cl, Cl, OMe, OMe,1-methyloxy-1-cyclohexylmethyl), (B1441, Cl, Cl, OMe, OMe,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B1442, Cl, Cl, OMe, OMe,1-ethyloxyethyl), (B1443, Cl, Cl, OMe, OMe, 1-ethyloxypropyl), (B1444,Cl, Cl, OMe, OMe, 1-(4-ethyloxybutyloxy)propyl), (B1445, Cl, Cl, OMe,OMe, 1-ethyloxybutyl), (B1446, Cl, Cl, OMe, OMe,1-ethyloxy-2-methylpropyl), (B1447, Cl, Cl, OMe, OMe, 1-ethyloxypentyl),(B1448, Cl, Cl, OMe, OMe, 1-ethyloxy-3-methylbutyl), (B1449, Cl, Cl,OMe, OMe, 1-ethyloxy-2,2-dimethylpropyl), (B1450, Cl, Cl, OMe, OMe,1-ethyloxyhexyl), (B1451, Cl, Cl, Ole, OMe,1-ethyloxy-3,3-dimethylbutyl), (B1452, Cl, Cl, OMe, OMe,1-ethyloxyheptyl), (B1453, Cl, Cl, OMe, OMe, 1-ethyloxyoctyl), (B1454,Cl, Cl, OMe, OMe, 1-ethyloxynonyl), (B1455, Cl, Cl, OMe, OMe,1-ethyloxydecyl), (B1456, Cl, Cl, OMe, OMe, 1-ethyloxyundecyl), (B1457,Cl, Cl, OMe, OMe, 1-ethyloxydodecyl), (B1458, Cl, Cl, OMe, OMe,1-ethyloxy-1-cyclohexylmethyl), (B1459, Cl, Cl, OMe, OMe,1-n-propyloxyethyl), (B1460, Cl, Cl, OMe, OMe, 1-n-propyloxypropyl),(B1461, Cl, Cl, OMe, OMe, 3-n-propyloxypropyl), (B1462, Cl, Cl, OMe,OMe, 1-n-propyloxybutyl), (B1463, Cl, Cl, OMe, OMe,1,4-di(n-propyloxy)butyl), (B1464, Cl, Cl, OMe, OMe,1-n-propyloxy-2-methylpropyl), (B1465, Cl, Cl, OMe, OMe,1-n-propyloxypentyl), (B1466, Cl, Cl, OMe, OMe,1-n-propyloxy-3-methylbutyl), (B1467, Cl, Cl, OMe, OMe,1-n-propyloxy-2,2-dimethylpropyl), (B1468, Cl, Cl, OMe, OMe,1-n-propyloxyhexyl), (B1469, Cl, Cl, OMe, OMe,1-n-propyloxy-3,3-dimethylbutyl), (B1470, Cl, Cl, OMe, OMe,1-n-propyloxyheptyl), (B1471, Cl, Cl, OMe, OMe, 1-n-propyloxyoctyl),(B1472, Cl, Cl, OMe, OMe, 1-n-propyloxynonyl), (B1473, Cl, Cl, OMe, OMe,1-n-propyloxydecyl), (B1474, Cl, Cl, OMe, OMe, 1-n-propyloxyundecyl),(B1475, Cl, Cl, OMe, OMe, 1-n-propyloxydodecyl), (B1476, Cl, Cl, OMe,OMe, 1-n-propyloxy-1-cyclohexylmethyl), (B1477, Cl, Cl, OMe, OMe,1-isopropyloxyethyl), (B1478, Cl, Cl, OMe, OMe, 1-isopropyloxypropyl),(B1479, Cl, Cl, OMe, OMe, 3-isopropyloxypropyl), (B1480, Cl, Cl, OMe,OMe, 1-isopropyloxybutyl), (B1481, Cl, Cl, OMe, OMe,1-isopropyloxy-2-methylpropyl), (B1482, Cl, Cl, OMe, OMe,1-isopropyloxypentyl), (B1483, Cl, Cl, OMe, OMe,1-isopropyloxy-3-methylbutyl), (B1484, Cl, Cl, OMe, OMe,1-isopropyloxy-2,2-dimethylpropyl), (131485, Cl, Cl, OMe, OMe,1-isopropyloxyhexyl), (B1486, Cl, Cl, OMe, OMe,1-isopropyloxy-3,3-dimethylbutyl), (31487, Cl, Cl, OMe, OMe,1-isopropyloxyheptyl), (31488, Cl, Cl, OMe, OMe, 1-isopropyloxyoctyl),(B1489, Cl, Cl, OMe, OMe, 1-isopropyloxynonyl), (B1490, Cl, Cl, OMe,OMe, 1-isopropyloxydecyl), (B1491, Cl, Cl, OMe, OMe,1-isopropyloxyundecyl), (B1492, Cl, Cl, OMe, OMe,1-isopropyloxydodecyl), (B1493, Cl, Cl, OMe, OMe,1-isopropyloxy-1-cyclohexylmethyl), (B1494, Cl, Cl, OMe, OMe,1-n-butyloxyethyl), (B1495, Cl, Cl, OMe, OMe, 1-n-butyloxypropyl),(B1496, Cl, Cl, OMe, OMe, 3-n-butyloxypropyl), (B1497, Cl, Cl, OMe, OMe,1-n-butyloxybutyl), (B1498, Cl, Cl, OMe, OMe, 1,4-di(n-butyloxy)butyl),(B1499, Cl, Cl, OMe, OMe, 1-n-butyloxy-2-methylpropyl), (B1500, Cl, Cl,OMe, OMe, 1-n-butyloxypentyl), (B1501, Cl, Cl, OMe, OMe,1-n-butyloxy-3-methylbutyl), (B1502, Cl, Cl, OMe, OMe,1-n-butyloxy-2,2-dimethylpropyl), (B1503, Cl, Cl, OMe, OMe,1-n-butyloxyhexyl), (B1504, Cl, Cl, OMe, OMe,1-n-butyloxy-3,3-dimethylbutyl), (B1505, Cl, Cl, OMe, OMe,1-n-butyloxyheptyl), (B1506, Cl, Cl, OMe, OMe, 1-n-butyloxyoctyl),(B1507, Cl, Cl, OMe, OMe, 1-n-butyloxynonyl), (B1508, Cl, Cl, OMe, OMe,1-n-butyloxydecyl), (B1509, Cl, Cl, OMe, OMe, 1-n-butyloxyundecyl),(B1510, Cl, Cl, OMe, OMe, 1-n-butyloxydodecyl), (B1511, Cl, Cl, OMe,OMe, 1-n-butyloxy-1-cyclohexylmethyl), (B1512, Cl, Cl, OMe, OMe,1-isobutyloxyethyl), (B1513, Cl, Cl, OMe, OMe, 1-isobutyloxypropyl),(B1514, Cl, Cl, OMe, OMe, 1-isobutyloxybutyl), (B1515, Cl, Cl, OMe, OMe,1-isobutyloxy-2-methylpropyl), (B1516, Cl, Cl, OMe, OMe,1-isobutyloxypentyl), (B1517, Cl, Cl, OMe, OMe,1-isobutyloxy-3-methylbutyl), (B1518, Cl, Cl, OMe, OMe,1-isobutyloxy-2,2-dimethylpropyl), (B1519, Cl, Cl, OMe, OMe,1-isobutyloxyhexyl), (B1520, Cl, Cl, OMe, OMe,1-isobutyloxy-3,3-dimethylbutyl), (B1521, Cl, Cl, OMe, OMe,1-isobutyloxyheptyl), (B1522, Cl, Cl, OMe, OMe, 1-isobutyloxyoctyl),(B1523, Cl, Cl, OMe, OMe, 1-isobutyloxyynonyl), (B1524, Cl, Cl, OMe,OMe, 1-isobutyloxydecyl), (B1525, Cl, Cl, OMe, OMe,1-isobutyloxyundecyl), (B1526, Cl, Cl, OMe, OMe, 1-isobutyloxydodecyl),(B1527, Cl, Cl, OMe, OMe, 1-isobutyloxy-1-cyclohexylmethyl), (B1528, Cl,Cl, OMe, OMe, 1-t-butyloxyethyl), (B1529, Cl, Cl, OMe, OMe,1-t-butyloxypropyl), (B1530, Cl, Cl, OMe, OMe, 1-t-butyloxybutyl),(B1531, Cl, Cl, OMe, OMe, 1-t-butyloxy-2-methylpropyl), (B1532, Cl, Cl,OMe, OMe, 1-t-butyloxypentyl), (B1533, Cl, Cl, OMe, OMe,1-t-butyloxy-3-methylbutyl), (B1534, Cl, Cl, OMe, OMe,1-t-butyloxy-2,2-dimethylpropyl), (B1535, Cl, Cl, OMe, OMe,1-t-butyloxyhexyl), (B1536, Cl, Cl, OMe, OMe,1-t-butyloxy-3,3-dimethylbutyl), (B1537, Cl, Cl, OMe, OMe,1-t-butyloxyheptyl), (B1538, Cl, Cl, OMe, OMe, 1-t-butyloxyoctyl),(B1539, Cl, Cl, OMe, OMe, 1-t-butyloxynonyl), (B1540, Cl, Cl, OMe, OMe,1-t-butyloxydecyl), (B1541, Cl, Cl, OMe, OMe, 1-t-butyloxyundecyl),(B1542, Cl, Cl, OMe, OMe, 1-t-butyloxydodecyl), (B1543, Cl, Cl, OMe,OMe, 1-t-butyloxy-1-cyclohexylmethyl), (B1544, Cl, Cl, OMe, OMe,1-n-pentyloxyethyl), (B1545, Cl, Cl, OMe, OMe, 1-n-pentyloxypropyl),(B1546, Cl, Cl, OMe, OMe, 3-n-pentyloxypropyl), (B1547, Cl, Cl, OMe,OMe, 1-n-pentyloxy-3-methylthiopropyl), (B1548, Cl, Cl, OMe, OMe,1-n-pentyloxybutyl), (B1549, Cl, Cl, OMe, OMe,1-n-pentyloxy-2-methylpropyl), (B1550, Cl, Cl, OMe, OMe,1-n-pentyloxypentyl), (B1551, Cl, Cl, OMe, OMe,1-n-pentyloxy-3-methylbutyl), (B1552, Cl, Cl, OMe, OMe,1-n-pentyloxy-2,2-dimethylpropyl), (B1553, Cl, Cl, OMe, OMe,1-n-pentyloxyhexyl), (B1554, Cl, Cl, OMe, OMe,1-n-pentyloxy-3,3-dimethylbutyl), (B1555, Cl, Cl, OMe, OMe,1-n-pentyloxyheptyl), (B1556, Cl, Cl, OMe, OMe, 1-n-pentyloxyoctyl),(B1557, Cl, Cl, OMe, OMe, 1-n-pentyloxynonyl), (B1558, Cl, Cl, OMe, OMe,1-n-pentyloxydecyl), (B1559, Cl, Cl, OMe, OMe, 1-n-pentyloxyundecyl),(B1560, Cl, Cl, OMe, OMe, 1-n-pentyloxydodecyl), (B1561, Cl, Cl, OMe,OMe, 1-n-pentyloxy-1-cyclohexylmethyl), (B1562, Cl, Cl, OMe, OMe,1-isopentyloxypropyl), (B1563, Cl, Cl, OMe, OMe, 1-neopentyloxyethyl),(B1564, Cl, Cl, OMe, OMe, 1-neopentyloxypropyl), (B1565, Cl, Cl, OMe,OMe, 3-neopentyloxypropyl), (B1566, Cl, Cl, OMe, OMe,1-neopentyloxybutyl), (B1567, Cl, Cl, OMe, OMe,1-neopentyloxy-2-methylpropyl), (B1568, Cl, Cl, OMe, OMe,1-neopentyloxypentyl), (B1569, Cl, Cl, OMe, OMe,1-neopentyloxy-3-methylbutyl), (B1570, Cl, Cl, OMe, OMe,1-neopentyloxy-2,2-dimethylpropyl), (B1571, Cl, Cl, OMe, OMe,1-neopentyloxyhexyl), (B1572, Cl, Cl, OMe, OMe,1-neopentyloxy-3,3-dimethylbutyl), (B1573, Cl, Cl, OMe, OMe,1-neopentyloxyheptyl), (B1574, Cl, Cl, OMe, OMe, 1-neopentyloxyoctyl),(B1575, Cl, Cl, OMe, OMe, 1-neopentyloxynonyl), (B1576, Cl, Cl, OMe,OMe, 1-neopentyloxydecyl), (B1577, Cl, Cl, OMe, OMe,1-neopentyloxyundecyl), (B1578, Cl, Cl, OMe, OMe,1-neopentyloxydodecyl), (B1579, Cl, Cl, OMe, OMe,1-neopentyloxy-1-cyclohexylmethyl), (B1580, Cl, Cl, OMe, OMe,1-n-hexyloxyethyl), (B1581, Cl, Cl, OMe, OMe, 1-n-hexyloxypropyl),(B1582, Cl, Cl, OMe, OMe, 3-n-hexyloxypropyl), (B1583, Cl, Cl, OMe, OMe,1-n-hexyloxybutyl), (B1584, Cl, Cl, OMe, OMe,1-n-hexyloxy-2-methylpropyl), (B1585, Cl, Cl, OMe, OMe,1-n-hexyloxypentyl), (B1586, Cl, Cl, OMe, OMe,1-n-hexyloxy-3-methylbutyl), (B1587, Cl, Cl, OMe, OMe,1-n-hexyloxy-2,2-dimethylpropyl), (B1588, Cl, Cl, OMe, OMe,1-n-hexyloxyhexyl), (B1589, Cl, Cl, OMe, OMe,1-n-hexyloxy-3,3-dimethylbutyl), (B1590, Cl, Cl, OMe, OMe,1-n-hexyloxyheptyl), (131591, Cl, Cl, OMe, OMe, 1-n-hexyloxyoctyl),(B1592, Cl, Cl, OMe, OMe, 1-n-hexyloxynonyl), (B31593, Cl, Cl, OMe, OMe,1-n-hexyloxydecyl), (B1594, Cl, Cl, OMe, OMe, 1-n-hexyloxyundecyl),(B1595, Cl, Cl, OMe, OMe, 1-n-hexyloxydodecyl), (B1596, Cl, Cl, OMe,OMe, 1-n-hexyloxy-1-cyclohexylmethyl), (B1597, Cl, Cl, OMe, OMe,3-isohexyloxypropyl), (B1598, Cl, Cl, OMe, OMe,3-(3,3-dimethylbutyloxy)propyl), (B1599, Cl, Cl, OMe, OMe,3-(2-cyclopentylethyloxy)propyl), (B1600, Cl, Cl, OMe, OMe,1-n-octyloxyethyl), (B1601, F, F, F, F, 1-methyloxy-3-n-hexyloxypropyl),(31602, F, F, Cl, F, 1-methyloxy-3-n-hexyloxypropyl), (B1603, F, F, F,F, 1-methyloxy-4-n-pentyloxybutyl), (B1604, F, F, Cl, F,1-methyloxy-4-n-pentyloxybutyl), (B1605, F, F, Me, F,1-methyloxy-2,2-dimethylpropyl), (B1606, F, F, Me, F,1-methyloxy-4-methylpentyl), (B1607, F, F, Me, F, 1-methyloxyheptyl),(B1608, F, F, Me, F, 1-methyloxyoctyl), (B1609, F, F, Me, F,1-methyloxynonyl), (B1610, F, F, Me, F, 1-methyloxydecyl), (B1611, F, F,Me, F, 1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B1612, F, F, Me, F,1-(4-ethyloxybutyloxy)propyl), (B1613, F, F, Me, F, 1-ethyloxypentyl),(B1614, F, F, Me, F, 1-n-propyloxybutyl), (B1615, F, F, Me, F,1-n-propyloxypentyl), (B1616, F, F, Me, F, 1-n-butyloxyethyl), (B1617,F, F, Me, F, 1-n-butyloxypropyl), (B1618, F, F, Me, F,3-n-butyloxypropyl), (B1619, F, F, Me, F, 1-n-butyloxybutyl), (B1620, F,F, Me, F, 1,4-di(n-butyloxy)butyl), (B1621, F, F, Me, F,1-n-butyloxypentyl), (B1622, F, F, Me, F, 1-n-pentyloxyethyl), (B1623,F, F, Me, F, 1-n-pentyloxypropyl), (B1624, F, F, Me, F,3-n-pentyloxypropyl), (B1625, F, F, Me, F,1-n-pentyloxy-3-methylthiopropyl), (B1626, F, F, Me, F,1-n-pentyloxybutyl), (B1627, F, F, Me, F, 1-n-pentyloxypentyl), (B1628,F, F, Me, F, 1-n-pentyloxy-2,2-dimethylpropyl), (B1629, F, F, Me, F,1-n-pentyloxy-1-cyclohexylmethyl), (B1630, F, F, Me, F,1-isopentyloxypropyl), (B1631, F, F, Me, F, 3-neopentyloxypropyl),(B1632, F, F, Me, F, 1-n-hexyloxypropyl), (B1633, F, F, Me, F,3-n-hexyloxypropyl), (B1634, F, F, Me, F, 3-isohexyloxypropyl), (B1635,F, F, Me, F, 3-(3,3-dimethylbutyloxy)propyl), (B1636, F, F, Me, F,3-(2-cyclopentylethyloxy)propyl), (B1637, F, F, Me, F,1-n-octyloxyethyl), (B1638, Cl, Cl, Me, F,1-methyloxy-2,2-dimethylpropyl), (B1639, Cl, Cl, Me, F,1-methyloxyhexyl), (B1640, Cl, Cl, Me, F, 1-methyloxy-4-methylpentyl),(B1641, Cl, Cl, Me, F, 1-methyloxyheptyl), (B1642, Cl, Cl, Me, F,1-methyloxyoctyl), (B1643, Cl, Cl, Me, F, 3-methyloxyoctyl), (B1644, Cl,Cl, Me, F, 1-methyloxynonyl), (B1645, Cl, Cl, Me, F, 1-methyloxydecyl),(B1646, Cl, Cl, Me, F, 1-methyloxyundecyl), (B1647, Cl, Cl, Me, F,1-(4-ethyloxybutyloxy)propyl), (B1648, Cl, Cl, Me, F, 1-ethyloxypentyl),(B1649, Cl, Cl, Me, F, 1-ethyloxy-3,3-dimethylbutyl), (B1650, Cl, Cl,Me, F, 1-n-propyloxyethyl), (B1651, Cl, Cl, Me, F, 1-n-propyloxypropyl),(B1652, Cl, Cl, Me, F, 3-n-propyloxypropyl), (B1653, Cl, Cl, Me, F,1-n-propyloxybutyl), (B1654, Cl, Cl, Me, F, 1,4-di(n-propyloxy)butyl),(B1655, Cl, Cl, Me, F, 1-n-propyloxypentyl), (B1656, Cl, Cl, Me, F,3-isopropyloxypropyl), (B1657, Cl, Cl, Me, F, 1-n-butyloxyethyl),(B1658, Cl, Cl, Me, F, 1-n-butyloxypropyl), (B1659, Cl, Cl, Me, F,3-n-butyloxypropyl), (B1660, Cl, Cl, Me, F, 1-n-butyloxybutyl), (B1661,Cl, Cl, Me, F, 1-n-butyloxypentyl), (B1662, Cl, Cl, Me, F,1-n-pentyloxypropyl), (B1663, Cl, Cl, Me, F, 3-n-pentyloxypropyl),(B1664, Cl, Cl, Me, F, 1-n-pentyloxy-3-methylthiopropyl), (B1665, Cl,Cl, Me, F, 1-n-pentyloxybutyl), (B1666, Cl, Cl, Me, F,1-n-pentyloxypentyl), (B1667, Cl, Cl, Me, F, 1-isopentyloxypropyl),(B1668, Cl, Cl, Me, F, 3-neopentyloxypropyl), (B13669, Cl, Cl, Me, F,1-n-hexyloxypropyl), (B1670, Cl, Cl, Me, F, 3-n-hexyloxypropyl), (B1671,Cl, Cl, Me, F, 3-isohexyloxypropyl), (B1672, Cl, Cl, Me, F,3-(3,3-dimethylbutyloxy)propyl), (B1673, Cl, Cl, Me, F,3-(2-cyclopentylethyloxy)propyl), (B1674, Cl, Cl, Me, F,1-n-octyloxyethyl), (B1675, Me, Me, Me, F,1-methyloxy-3-n-hexyloxypropyl), (B1676, Me, Me, Me, F,1-methyloxy-4-n-pentyloxybutyl), (B1677, Me, Me, Me, F,1-methyloxy-2,2-dimethylpropyl), (B1678, Me, Me, Me, F,1-methyloxyhexyl), (B1679, Me, Me, Me, F, 1-methyloxy-4-methylpentyl),(B1680, Me, Me, Me, F, 1-methyloxyheptyl), (B1681, Me, Me, Me, F,1-methyloxyoctyl), (B1682, Me, Me, Me, F, 3-methyloxyoctyl), (B1683, Me,Me, Me, F, 1-methyloxynonyl), (B1684, Me, Me, Me, F, 1-methyloxydecyl),(B1685, Me, Me, Me, F, 1-methyloxyundecyl), (B1686, Me, Me, Me, F,1-(4-ethyloxybutyloxy)-1-cyclohexylmethyl), (B1687, Me, Me, Me, F,1-(4-ethyloxybutyloxy)propyl), (B1688, Me, Me, Me, F, 1-ethyloxypentyl),(B1689, Me, Me, Me, F, 1-ethyloxy-3,3-dimethylbutyl), (B1690, Me, Me,Me, F, 1-n-propyloxyethyl), (B1691, Me, Me, Me, F, 1-n-propyloxypropyl),(B1692, Me, Me, Me, F, 3-n-propyloxypropyl), (B1693, Me, Me, Me, F,1-n-propyloxybutyl), (B1694, Me, Me, Me, F, 1,4-di(n-propyloxy)butyl),(B1695, Me, Me, Me, F, 1-n-propyloxypentyl), (B1696, Me, Me, Me, F,3-isopropyloxypropyl), (13697, Me, Me, Me, F, 1-n-butyloxyethyl),(B1698, Me, Me, Me, F, 1-n-butyloxypropyl), (B1699, Me, Me, Me, F,3-n-butyloxypropyl), (B11700, Me, Me, Me, F, 1-n-butyloxybutyl), (B1701,Me, Me, Me, F, 1,4-di(n-butyloxy)butyl), (B1702, Me, Me, Me, F,1-n-butyloxypentyl), (B1703, Me, Me, Me, F, 1-n-pentyloxyethyl), (B1704,Me, Me, Me, F, 1-n-pentyloxypropyl), (B1705, Me, Me, Me, F,3-n-pentyloxypropyl), (B1706, Me, Me, Me, F,1-n-pentyloxy-3-methylthiopropyl), (B1707, Me, Me, Me, F,1-n-pentyloxybutyl), (B1708, Me, Me, Me, F, 1-n-pentyloxypentyl),(B1709, Me, Me, Me, F, 1-n-pentyloxy-2,2-dimethylpropyl), (B1710, Me,Me, Me, F, 1-n-pentyloxy-1-cyclohexylmethyl), (B1711, Me, Me, Me, F,1-isopentyloxypropyl), (B1712, Me, Me, Me, F, 3-neopentyloxypropyl),(B1713, Me, Me, Me, F, 1-n-hexyloxypropyl), (B1714, Me, Me, Me, F,3-n-hexyloxypropyl), (B1715, Me, Me, Me, F, 3-isohexyloxypropyl),(B1716, Me, Me, Me, F, 3-(3,3-dimethylbutyloxy)propyl), (B1717, Me, Me,Me, F, 3-(2-cyclopentylethyloxy)propyl), (B1718, Me, Me, Me, F,1-n-octyloxyethyl), (B1719, Me, Me, Me, F, 1-methyloxyhexyl), (B1720,Me, Me, Me, F, 3-methyloxyoctyl), (B1721, Me, Me, Me, F,1-methyloxyundecyl), (B1722, Me, Me, Me, F,1-ethyloxy-3,3-dimethylbutyl), (B1723, Me, Me, Me, F,1-n-propyloxyethyl), (B1724, Me, Me, Me, F, 1-n-propyloxypropyl),(B1725, Me, Me, Me, F, 3-n-propyloxypropyl), (B1726, Me, Me, Me, F,1,4-di(n-propyloxy)butyl), (B1727, Me, Me, Me, F, 3-isopropyloxypropyl)

Example 584 Synthesis of3-(4-{4-[3-(1-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbomzyl}-2,6-difluorophenyl)-2-methylacrylicacid disodium salt (C1)

To a suspension of methanol (100 mL) solution of3-(4-{4-[3-(1-n-butyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbonyl}-2,6-difluorophenyl)-2-methylacrylicacid (3.22 mg) was added 2M sodium hydroxide aqueous solution (6.06 mL).After stirring for 1 h, n-hexylaldehyde (5.88 mL) was added to thereaction mixture. After methanol was evaporated under reduced pressure,the obtained residue was redissolved by adding water (40 mL). The watersolution was freeze drying to obtain the compound (C1) 3.40 g.

1H-NMR(DMSO-d6) 8.05-8.11 (m, 1H), 7.69-7.75 (m, 1H), 7.22-7.29 (m, 2H),7.15 (d, 1H, J=3.1 Hz), 7.03 (s, 1H), 4.56-4.60 (m, 1H), 3.31 (t, 2H,J=6.3 Hz), 1.65-1.80 (m, 5H), 1.45-1.55 (m, 2H), 1.30-1.40 (m, 2H),0.83-0.91 (m, 6H).

C2 to C6 were synthesized by similar method described above.

Example 585 Synthesis of3-[2,6-dichloro-4-(4-{3-[3-(2-ethylbutyloxy)propyl]-2-fluorophenyl}thiazol-2-ylcarbonyl)phenyl]-2-methylacrylicacid disodium salt (C2)

1H-NMR(DMSO-d6) 8.11 (s, 2H), 7.97-8.03 (m, 2H), 7.11-7.18 (m, 1H),3.26-3.41 (m, 4H), 2.72 (t, 2H, J=7.3 Hz), 1.78-1.87 (m, 2H), 1.62 (s,3H), 1.24-1.62 (m, 5H), 0.86 (t, 6H, J=7.3 Hz).

Example 586 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxydecyl)phenyl]thiazol-2-ylcarbonyl}phenyl)-2-methylacrylicacid disodium salt (C3)

1H-NMR(DMSO-d6) 8.06-8.17 (m, 3H), 7.20-7.28 (m, 2H), 7.13 (d, 1H, J=3.2Hz), 7.06 (s, 1H), 4.53-4.58 (m, 1H), 3.17 (s, 3H), 1.60-1.82 (m, 5H),1.23 (m, 14H), 0.86 (t, 3H, J=7.0 Hz).

Example 587 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(1-methyloxyoctyl)phenyl]thiazol-2-ylcarbonyl}phenyl)-2-methylacrylicacid disodium salt (C4)

1H-NMR(DMSO-d6) 8.06-8.12 (m, 3H), 7.23-7.29 (m, 2H), 7.16 (d, 1H, J=3.1Hz), 7.12 (s, 1H), 4.53-4.57 (m, 1H), 3.17 (s, 3H), 1.60-1.82 (m, 5H),1.23-1.37 (m, 10H), 0.84 (t, 3H, J=6.6 Hz).

Example 588 Synthesis of3-(2,6-dichloro-4-{4-[2-fluoro-3-(3-n-propyloxypropyl)phenyl]thiazol-2-ylcarbonyl}phenyl)-2-methylacrylicacid disodium salt (C5)

1H-NMR(DMSO-d6) 8.13 (s, 2H), 7.98-8.04 (m, 1H), 7.12-7.17 (m, 4H), 3.40(t, 2H, J=6.3 Hz), 3.30 (t, 2H, J=6.6 Hz), 7.20 (t, 2H, J=7.5 Hz),1.78-1.88 (m, 2H), 1.64 (s, 3H), 1.47-1.64 (m, 2H), 0.88 (t, 3H, J=7.5Hz).

Example 589 Synthesis of3-(4-{4-[3-(3-ethyloxypropyl)-2-fluorophenyl]thiazol-2-ylcarbonyl}-2,6-difluorophenyl)-2-methylacrylicacid disodium salt (C6)

1H-NMR(DMSO-d6) 7.99-8.05 (m, 1H), 7.72-7.78 (m, 2H), 7.12-7.19 (m, 3H),7.07 (s, 1H), 3.38-3.47 (m, 4H), 2.69-2.74 (m, 2H), 1.76-1.87 (m, 5H),1.13 (t, 3H, J=7.0 Hz).

Test Examples Test Example 1 Isolation and Purification ofThrombopoietin (TPO)

Human TPO (hTPO) and murine TPO (mTPO) were purchased from R&D Systems.

Test Example 2 The Thrombopoietic Activity

The TPO dependent BaF/hTPOR cell line which was established byintroducing human TPO receptor (hTPOR) into BaF-B03 cells according toCollins et al (J. Cell. Physiol., 137:293-298 (1988)) was used to testthe thrombopoietic activity of the present compound. The DNA sequencesand encoded peptide sequences for human hTPOR have been described byVigon et al (Proc. Natl. Acad. Sci. USA, 89:5640-5644 (1992)). TPO dosenot have any ability to support proliferation of interleukin-3 dependentparental cell line BaF-B03. BAF/hTPOR cells were maintained in RPMImedium and WEHI-3B conditioned medium as a source of murineinterleukin-3 (IL-3). These cells were washed and resuspended in RPMImedium without a source of murine IL-3 and seeded into each well of96-well microtiter plates at a density of 5×10⁴ cells per well in theabsence or presence of various concentration of hTPO or the presentcompound. After incubation at 37° C. for 20 hours in the 5% CO₂incubator, 10% WST-1 reagent (Takara Biomedicals, Japan) was added toeach wells and the cells were further incubated for 4 hours. Theabsorbance at 450 nm was measured. Tables 1 and 2 exemplify the ED₅₀ fortested compounds of the present invention, wherein the ED₅₀ is the halfconcentration of the concentration showing the maximum thrombopoieticactivity.

TABLE 1 No. ED50(μM) A1 0.00227 A2 0.004 A3 0.004 A4 0.00180 A5 0.00191A6 0.00104 A7 0.00226 A8 0.0029 A9 0.0030 A10 0.0012 A11 0.00087 A120.0008 A1123 0.00727 A1308 0.0129 A1309 0.01278 A1310 0.0123 A13110.00886 A1312 0.01083 A1314 0.01251 A1315 0.01247 A1316 0.00529 A13170.01506 B1 0.0022 B2 0.004 B6 0.0024 B7 0.0036 B8 0.0040 B9 0.0016 B100.0019 B11 0.00081 B12 0.0021 B13 0.0010 B14 0.00073 B15 0.00073 B160.00077 B18 0.00057 B19 0.00073 B20 0.00081 B21 0.00067 B22 0.00114 B230.00123 B24 0.00197 B25 0.00093 B26 0.00039 B27 0.00075 B28 0.00079 B290.00203 B30 0.00078 B31 0.00085 B32 0.00303 B33 0.00333 B34 0.00099 B350.00077 B36 0.00063 B37 0.00088 B38 0.00062 B39 0.00101 B40 0.00088 B410.00067 B42 0.00034 B43 0.00165 B44 0.00127 B45 0.00136 B46 0.00128 B470.00280 B48 0.00223 B49 0.0013 B50 0.00080 B51 0.00068 B52 0.0017 B530.0014 B56 0.0027 B58 0.0015 B60 0.00075 B61 0.00076 B62 0.00076 B630.00020 B64 0.00119 B65 0.00104 B66 0.00091 B67 0.00048 B68 0.00082 B690.00078 B70 0.00043 B71 0.00100 B72 0.00078 B73 0.00135 B74 0.00080 B750.00077 B76 0.00298 B77 0.00306 B78 0.00097 B79 0.00077 B80 0.00070 B810.00139 B82 0.00107 B83 0.00072 B84 0.00102 B85 0.00088 B86 0.00063 B870.00062 B88 0.00311 B89 0.00151 B90 0.00115 B91 0.00102 B93 0.00091 B940.00097 B95 0.00082 B96 0.00078 B97 0.00094 B98 0.00073 B99 0.00059 B1000.00068 B101 0.0019 B347 0.01872 B349 0.01679 B354 0.0032 B355 0.0033B380 0.02325 B397 0.00252 B418 0.0063 B419 0.01455 B425 0.00201 B4840.00129 B488 0.01588 B505 0.012 B519 0.00103 B521 0.01688 B1054 0.01994B1059 0.0032 B1060 0.0039 B1102 0.00286 B1122 0.00825 B1124 0.01584B1437 0.0065 B1438 0.0063 B1799 0.01732 B1800 0.00304 B1833 0.01899B1848 0.01594 B1851 0.01684 B1852 0.01648 B1877 0.01304 B1884 0.01685B1890 0.01815 B1892 0.01164 B1916 0.01286 B1920 0.01452 B1922 0.01359B1925 0.01841 B1926 0.01556 B1927 0.01944 B1928 0.01257 B1933 0.00788B1934 0.01304 B1936 0.01711 B1938 0.01268 B1940 0.01883 B1945 0.01927B1948 0.01091 B1949 0.01316 B1952 0.01013 B1953 0.01007 B1954 0.01294B1955 0.01165 B1956 0.01507 B1957 0.01275 B1958 0.00757 B1959 0.01126B1960 0.01014 B1990 0.01214 B1991 0.01323 B1992 0.01305 B1993 0.01392B1994 0.01424 B1995 0.01093 B1997 0.01553 B1998 0.00835 B1999 0.01324B2001 0.01942 B2004 0.01394 B2005 0.01033 B2020 0.01094 B2021 0.00609B2022 0.01563 B2023 0.00645 B2024 0.00996 B2025 0.0032 B2026 0.01259B2027 0.01259 B2028 0.01143 B2099 0.00291

TABLE 2 No. ED50(μM) B380 0.02325 B1836 0.02102 B1849 0.02245 B18540.02443 B1855 0.02133 B1861 0.02282 B1863 0.02276 B1878 0.02119 B18860.02208 B1900 0.02316 B1901 0.02425 B1904 0.02457 B1905 0.02665 B19080.02628 B1909 0.02586 B1918 0.02102 B1919 0.02793 B1923 0.02017 B19240.02058 B1929 0.02584 B1935 0.0254 B1937 0.02308 B1941 0.02413 B19510.02226 B1963 0.02858 B2000 0.0205 B2003 0.02271 B2012 0.02419 B20180.02351

Formulation Example Formulation Example 1

Granules are prepared using the following ingredients.

Ingredients The compound represented by the formula (I)  10 mg Lactose700 mg Corn starch 274 mg HPC-L  16 mg 1000 mg 

The compound represented by the formula (I) and lactose are made passthrough a 60 mesh sieve. Corn starch is made pass through a 120 meshsieve. They are mixed by a twin shell blender. An aqueous solution ofHPC-L (low mucosity hydroxypropylcellulose) is added to the mixture andthe resulting mixture is kneaded, granulated (by the extrusion with poresize 0.5 to 1 mm mesh), and dried. The dried granules thus obtained aresieved by a swing sieve (12/60 mesh) to yield the granules.

Formulation 2

Powders for filling capsules are prepared using the followingingredients.

Ingredients The compound represented by the formula (I) 10 mg Lactose 79mg Corn starch 10 mg Magnesium stearate  1 mg 100 mg 

The compound represented by the formula (I) and lactose are made passthrough a 60 mesh sieve. Corn starch is made pass through a 120 meshsieve. These ingredients and magnesium stearate are mixed by a twinshell blender. 100 mg of the 10-fold trituration is filled into a No. 5hard gelatin capsule.

Formulation 3

Granules for filling capsules are prepared using the followingingredients.

Ingredients The compound represented by the formula (I) 15 mg Lactose 90mg Corn starch 42 mg HPC-L  3 mg 150 mg 

The compound represented by the formula (I) and lactose are made passthrough a 60 mesh sieve. Corn starch is made pass through a 120 meshsieve. After mixing them, an aqueous solution of HPC-L is added to themixture and the resulting mixture is kneaded, granulated, and dried.After the dried granules are lubricated, 150 mg of that are filled intoa No. 4 hard gelatin capsule. Formulation 4

Tablets are prepared using the following ingredients.

Ingredients The compound represented by the formula (I) 10 mg Lactose 90mg Microcrystal cellulose 30 mg CMC-Na 15 mg Magnesium stearate  5 mg150 mg 

The compound represented by the formula (I), lactose, microcrystalcellulose, and CMC—Na (carboxymethylcellulose sodium salt) are made passthrough a 60 mesh sieve and then mixed. The resulting mixture is mixedwith magnesium stearate to obtain the mixed powder for the tabletformulation. The mixed powder is compressed to yield tablets of 150 mg.

Formulation 5

Intravenous formulations are prepared using the following ingredients.

Ingredients The compound represented by the formula (I) 100 mg Saturatedfattyacid glyceride 1000 mlUsually a solution of ingredients above described is administeredintravenously to a patient by the speed of 1 ml/min.

INDUSTRIAL APPLICABILITY

The compounds of the present invention have thrombopoietin receptoragonism and are useful as the treating or preventing agent for hemopathyaccompanied with unusual count of platelet, for example,thrombocytopenia and the like

1-12. (canceled)
 13. A compound represented by the general formula (III):

wherein R^(E) is C1-C15 alkyl optionally substituted with one or two substituent(s) selected from substituent group C, C2-C15 alkynyl optionally substituted with one or two substituent(s) selected from substituent group C, or C1-C15 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group C; Z is straight-chain C1-C4 alkylene optionally substituted with C1-C8 alkyl, which may contain an optionally substituted heteroatom(s) or straight-chain C2-C4 alkenylene optionally substituted with C1-C8 alkyl, which may contain an optionally substituted heteroatom(s) R⁶ and R⁷ are each independently halogen atom or C1-C3 alkyl; R⁸ is halogen atom, C1-C3 alkyl, or C1-C3 alkyloxy; substituent group C consists of halogen atom, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, phenyl, naphthyl, pyridyl, oxolanyl, cyano, C1-C8 alkyloxy, C2-C8 alkenyloxy, C2-C8 alkynyloxy, C3-C8 cycloalkyl-C1-C8 alkyloxy, phenyl-C1-C8 alkyloxy, naphthyl-C1-C8 alkyloxy, C1-C8 alkyloxy-C1-C8 alkyloxy, (C1-C8 alkyloxy-C1-C8 alkyloxy)C1-C8 alkyloxy, di(C1-C8 alkyloxy)C1-C8 alkyloxy, oxolanyl-C1-C8 alkyloxy, haloC1-C8 alkyloxy, C3-C8 cycloalkyloxy, amino optionally substituted with C1-C8 alkyl, C1-C8 alkylthio, and C1-C8 alkylthio-C1-C8 alkyloxy; a pharmaceutically acceptable salt, or solvate thereof.
 14. A compound of claim 13, wherein both of R⁶ and R⁷ are fluorine atom or chlorine atom, a pharmaceutically acceptable salt, or solvate thereof.
 15. A compound of claim 13, wherein R⁸ is methyl or methyloxy, a pharmaceutically acceptable salt, or solvate thereof.
 16. A compound of claim 13, wherein Z is C1-C4 alkylene, —O—(C1-C3 alkylene)- or —(C1-C3 alkylene)-O—, a pharmaceutically acceptable salt, or solvate thereof.
 17. A compound of any one of claims 13 to 16, wherein R^(E) is C1-C10 alkyl optionally substituted with one or two substituent(s) selected from substituent group C, C2-CG 0 alkynyl optionally substituted with one or two substituent(s) selected from substituent group C, or C1-C10 alkyloxy optionally substituted with one or two substituent(s) selected from substituent group C, a pharmaceutically acceptable salt, or solvate thereof.
 18. A compound of claim 13, wherein both of R⁶ and R⁷ are fluorine atom or chlorine atom, R⁸ is methyl or methyloxy, R^(E) is C1-C8 alkyl optionally substituted with one or two C1-C6 alkyloxy, Z is C1-C2 alkylene, a pharmaceutically acceptable salt, or solvate thereof. 19-23. (canceled)
 24. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 13 to 16 or
 18. 25. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 13 to 16 or 18, in an amount effective for exhibiting thrombopoietin receptor agonism.
 26. A pharmaceutical composition containing a compound as an active ingredient, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 13 to 16 or 18, in an amount effective for modifying platelet production.
 27. (canceled)
 28. A method for treating or preventing hemopathy in a mammal, including a human, in need thereof, comprising administering to said mammal a compound, a pharmaceutically acceptable salt, or solvate thereof of any one of claims 13 to 16 or 18 in an amount effective for modifying platelet production. 